Biliary cannulation is a critical component of endoscopic retrograde cholangiopancreatography (ERCP). When standard methods fail, needle-knife precut sphincterotomy (NKPS) is commonly employed. This systematic review and meta-analysis evaluated the safety and efficacy of using NKPS as a primary technique. Electronic databases were searched for studies published between January 2000 and November 2024 that assessed outcomes of primary precut techniques. "Primary precut" was defined as needle-knife sphincterotomy performed as the initial approach without any prior standard cannulation attempts. Pooled proportions were calculated using random-effects models, and heterogeneity was assessed using the Q-test and the I² statistic. The mean patient age was 57.95 years (standard deviation [SD], 7.59), and 53.23% were female. The cannulation success rate was 96.50% (95% confidence interval [CI], 94.90-97.60) with no heterogeneity (Q, 7.10; df, 8; I²=0%; p=0.935). The rates of adverse events were as follows: post-ERCP pancreatitis, 1.90% (95% CI, 1.20-3.10; I²=0; p =0.942); bleeding, 2.60% (95% CI, 1.70-4.00, I²=0; p=0.725); cholangitis, 1.50% (95% CI, 0.60-3.60; I²=45.27; p=0.067); and perforation, 0.90% (95% CI, 0.40-1.90; I²=0; p=0.948). The overall adverse event rate was 9.70% (95% CI, 5.70-16.10; I²=83.39; p<0.001). Primary precut sphincterotomy appears to be an effective and safe technique for biliary cannulation in ERCP. These findings support its consideration as a viable first-line approach in appropriate clinical settings.

Predictors of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Comprehensive Systematic Review and Meta-analysis.

Abstract Introduction Endoscopic retrograde cholangiopancreatography (ERCP) is a key procedure in managing biliary and pancreatic disorders. In cases of difficult cannulation (DC), when standard cannulation techniques (SCT) fail, precut sphincterotomy (PS) may be used as an alternative technique, often by experienced endoscopists. The aim of this study was to compare outcomes of PS versus SCT in cases of DC, regarding complication rates and successful cannulation. Method Data were retrieved from the Swedish GallRiks Registry from September 2016 to December 2023. A total of 30,561 ERCPs, performed as index ERCPs without rendezvous technique, were identified and cross-checked. Univariable and multivariable logistic regression were conducted. We used generalized estimating equations to adjust for endoscopist- and hospital volumes. Result Altogether 9,909 procedures were classified as DC among which 3,005 (30%) were performed with PS, compared to 434 (2%) of 20,218 in the non-DC group. In DC PS was not associated with increased risk of procedure related complications (pancreatitis, cholangitis, bleeding, bile leakage or perforation). The rate of successful cannulation in DC was 87.9% when SCT were used and 70.4% when PS was performed. Discussion PS is a safe technique in ERCP when cannulation is difficult and is not associated with an increased risk of complications compared to SCT.

Dental floss traction-assisted precut sphincterotomy for difficult biliary cannulation in elongated papilla

In single balloon-enteroscopy-assisted endoscopic retrograde cholangiopancreatography (SBE-assisted ERCP) for patients with surgically altered anatomies, precut sphincterotomy is performed as an advanced cannulation technique for difficult biliary cannulation cases. This study evaluated the safety and efficacy of precut sphincterotomy. The study included patients who underwent SBE-assisted ERCP on a naive papilla with surgically altered anatomies (excluding Billroth-I reconstruction) from April 2015 to December 2023. The success rate of biliary cannulation and the complication incidence were analyzed retrospectively. A total of 231 patients were included. Scope insertion to the duodenal papilla was possible in 204 cases (88.3%), and biliary cannulation was attempted in 198 cases (85.7%). Standard cannulation was successful in 132 cases (66.7%), while an additional 10 cases (5.1%) successfully cannulated using pancreatic guide wire-assisted biliary cannulation. An additional 28 cases (14.1%) were successfully cannulated using precut sphincterotomy. Therefore, the overall biliary cannulation success rate was 85.9% (170 of 198 cases). The success rate of precut sphincterotomy was 66.7% (28 of 42 cases). Intraoperative bleeding caused by precut sphincterotomy occurred in 11.9%, and other complications were present in 16.7% of cases. Precut sphincterotomy is a one of the valuable techniques in SBE-assisted ERCP for surgically altered anatomies.

Precut sphincterotomy is often performed when bile duct cannulation is difficult; however, the former has a higher risk of complications than conventional methods. Early precut reduces the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). This study aimed to determine the appropriate timing for precut sphincterotomy to minimize the incidence of PEP. This retrospective study analyzed 320 patients who underwent precut sphincterotomy during their first endoscopic retrograde cholangiopancreatography at a single center. The optimal precut timing was identified using receiver operating characteristic analysis. Patients were divided into an optimized precut group (≤12min, n=198) and a delayed group (>12min, n=122). The incidence and risk factors of PEP were evaluated using multivariate analyses. Receiver operating characteristic analysis identified 12.5min as the optimal cutoff for transitioning to precut sphincterotomy (area under the curve, 0.613; sensitivity, 61.5%; specificity, 63.9%). The incidence of PEP was significantly lower in the optimized precut group than in the delayed precut group (5.1%vs. 13.1%, p=0.02). Multivariate analysis identified delayed precut timing (odds ratio [OR], 3.134; p=0.04) and the absence of endoscopic pancreatic stenting (OR, 0.284; p=0.01) as independent risk factors for PEP. Precut sphincterotomy within 12.5min of a cannulation attempt reduces the risk of PEP while maintaining procedural safety. Additionally, endoscopic pancreatic stentingcan reduce PEP, even in precut scenarios.

Transpancreatic precut sphincterotomy with a novel highly rotatable sphincterotome in balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography.

Endoscopic Ultrasound-guided Rendezvous Technique versus Precut Sphincterotomy as Salvage Technique for Biliary Access: A Meta-Analysis

Background:Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a severe and deadly adverse event following ERCP. The ideal method for predicting PEP risk before ERCP has yet to be identified. We aimed to establish a simple PEP risk score model (SuPER model: Support for PEP Reduction) that can be applied before ERCP.Methods:This multicenter study enrolled 2074 patients who underwent ERCP. Among them, 1037 patients each were randomly assigned to the development and validation cohorts. In the development cohort, the risk score model for predicting PEP was established via logistic regression analysis. In the validation cohort, the performance of the model was assessed.Results:In the development cohort, five PEP risk factors that could be identified before ERCP were extracted and assigned weights according to their respective regression coefficients: –2 points for pancreatic calcification, 1 point for female sex, and 2 points for intraductal papillary mucinous neoplasm, a native papilla of Vater, or the pancreatic duct procedures (treated as ‘planned pancreatic duct procedures’ for calculating the score before ERCP). The PEP occurrence rate was 0% among low-risk patients (≤0 points), 5.5% among moderate-risk patients (1–3 points), and 20.2% among high-risk patients (4–7 points). In the validation cohort, the C statistic of the risk score model was 0.71 (95% CI 0.64–0.78), which was considered acceptable. The PEP risk classification (low, moderate, and high) was a significant predictive factor for PEP that was independent of intraprocedural PEP risk factors (precut sphincterotomy and inadvertent pancreatic duct cannulation) (OR 4.2, 95% CI 2.8–6.3; p&lt;0.01).Conclusions:The PEP risk score allows an estimation of the risk of PEP prior to ERCP, regardless of whether the patient has undergone pancreatic duct procedures. This simple risk model, consisting of only five items, may aid in predicting and explaining the risk of PEP before ERCP and in preventing PEP by allowing selection of the appropriate expert endoscopist and useful PEP prophylaxes.Funding:No external funding was received for this work.

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a severe and deadly adverse event following ERCP. The ideal method for predicting PEP risk before ERCP has yet to be identified. We aimed to establish a simple PEP risk score model (SuPER model: Support for PEP Reduction) that can be applied before ERCP. This multicenter study enrolled 2074 patients who underwent ERCP. Among them, 1037 patients each were randomly assigned to the development and validation cohorts. In the development cohort, the risk score model for predicting PEP was established via logistic regression analysis. In the validation cohort, the performance of the model was assessed. In the development cohort, five PEP risk factors that could be identified before ERCP were extracted and assigned weights according to their respective regression coefficients: -2 points for pancreatic calcification, 1 point for female sex, and 2 points for intraductal papillary mucinous neoplasm, a native papilla of Vater, or the pancreatic duct procedures (treated as 'planned pancreatic duct procedures' for calculating the score before ERCP). The PEP occurrence rate was 0% among low-risk patients (≤0 points), 5.5% among moderate-risk patients (1-3 points), and 20.2% among high-risk patients (4-7 points). In the validation cohort, the C statistic of the risk score model was 0.71 (95% CI 0.64-0.78), which was considered acceptable. The PEP risk classification (low, moderate, and high) was a significant predictive factor for PEP that was independent of intraprocedural PEP risk factors (precut sphincterotomy and inadvertent pancreatic duct cannulation) (OR 4.2, 95% CI 2.8-6.3; p<0.01). The PEP risk score allows an estimation of the risk of PEP prior to ERCP, regardless of whether the patient has undergone pancreatic duct procedures. This simple risk model, consisting of only five items, may aid in predicting and explaining the risk of PEP before ERCP and in preventing PEP by allowing selection of the appropriate expert endoscopist and useful PEP prophylaxes. No external funding was received for this work.

BackgroundAdverse events after endoscopic retrograde cholangiopancreatography (ERCP) are rare, and post-ERCP pancreatitis is a serious adverse event. This study aimed to determine the role of aggressive intravenous hydration with lactated Ringer’s solution at a specific volume with 20% human albumin before ERCP in reducing the incidence of post-ERCP pancreatitis.MethodsThis study was a single-centre randomized clinical trial. The participants were randomly assigned to two groups: those who received aggressive intravenous hydration with 20% human albumin and lactated Ringer's solution (intervention group), and those who received standard-volume intravenous hydration with lactated Ringer's solution (control group). The primary endpoint was post-ERCP pancreatitis. Participants and outcome assessors were blinded to treatment allocation. Comparison was performed using the chi-square, the Fisher’s exact, the Student’s t, or the Mann–Whitney U tests, where appropriate.ResultsOf 300 randomized participants, 149 and 144 participants from the intervention and control group were included in the analysis. There was no significant difference in the post-ERCP pancreatitis rate (n = 10; 6.7% versus n = 9; 6.3%, P = 0.873) between the intervention and control groups. High-risk procedures (that is pancreatic duct wiring, pancreatic duct injection, precut sphincterotomy, and balloon dilation of the ampulla) were significantly associated with post-ERCP pancreatitis compared with low-risk procedures (n = 15; 15% versus n = 4; 2.1%, P < 0.001). In the high-risk procedures population, the intervention and control groups had increased post-ERCP pancreatitis rates (P = 0.716). Two participants in each group developed pulmonary congestion.ConclusionAggressive peri-ERCP intravenous hydration with lactated Ringer's solution combined with 50 ml of 20% human albumin did not prevent post-ERCP pancreatitis. None of the subgroups presented with prophylactic effects.Trial registrationThai Clinical Trials Registry (TCTR20240405003)

BackgroundWhen cannulation is challenging during endoscopic retrograde cholangiopancreatography (ERCP), and the standard guidewire technique with sphincterotomy is unsuccessful, alternative cannulation techniques can be used to access the biliary tree. The purpose of this study was to compare the incidence of adverse events and cannulation success rates between transpancreatic sphincterotomy (TPS) and precut sphincterotomy (PCS).MethodsData from the Swedish Registry for Gallstone Surgery and ERCP (GallRiks), collected from 2011 to 2022, were analyzed. A total of 105,303 ERCP procedures were recorded in GallRiks during the study period. After exclusions, the study population consisted of 47,486 ERCP procedures. Of these, 4547 received PCS and 3273 received TPS. The remaining 39,666 ERCP procedures with conventional sphincterotomy served as the control group. The primary endpoints were successful cannulation and adverse events within 30 days.ResultsSuccessful cannulation was more frequent with the TPS technique than with the PCS technique (86.5% vs. 69.7%), but both groups had a lower cannulation rate than the control group (92.4%; OR-PCS 0.20, 95% CI 0.18–0.21; OR-TPS 0.58, 95% CI 0.52–0.64). The TPS group had a higher incidence of adverse events than the PCS group (24.1% vs. 18.8%) and both groups had a higher incidence of adverse events than the control group (15.5%; OR-PCS 1.25, 95% CI 1.15–1.36; OR-TPS 1.71, 95% CI 1.57–1.87). Adverse events for TPS were driven by a higher incidence of pancreatitis (10.5% vs. 6.4% vs. 4.5%; OR 2.53, 95% CI 2.23–2.86) and perforation (1.6% vs. 0.8% vs. 0.5%; OR 2.99, 95% CI 2.20–4.06) compared to both PCS and control.ConclusionTPS is more successful at cannulation than PCS; however, this success comes at a higher cost in terms of adverse events, particularly pancreatitis and perforation.Graphical abstract

Acute pancreatitis, which sometimes results in mortality, is a significant complication of endoscopic retrograde cholangiopancreatography (ERCP). Many studies have been conducted to predict and prevent post-ERCP pancreatitis (PEP), and meta-analyses have been reported that summarized these studies. However, many issues remain unresolved. Many risk factors for PEP have been reported, and it is rare for patients undergoing ERCP to have only one risk factor. The use of artificial intelligence may be important for analyzing complex and diverse risk factors. It is desirable to develop an alternative test for pancreatic enzymes that can predict the onset of PEP within 1 h after ERCP. The effectiveness of low-dose nonsteroidal anti-inflammatory drugs (NSAIDs) are controversial. Nitrate and tacrolimus are considered medications that have additional effects on NSAIDs and may be used for the prevention of PEP. Pancreatic stent placement with deliberate placement of the guidewire into the pancreatic duct may be more effective in preventing PEP. A comparison between transpancreatic sphincterotomy with deliberate guidewire placement into the pancreatic duct and needle-knife precut sphincterotomy is necessary. Early precutting is thought to be effective for the prevention of PEP, and the effectiveness of primary precut has been reported. However, the optimal timing of precut for the prevention of PEP has not been sufficiently discussed. Further research on prediction and prevention must be conducted to eliminate the mortality caused by PEP.

Background: This study aimed to evaluate whether the morphology of the duodenal major papilla is linked to transpancreatic precut sphincterotomy (TPS) failure. Methods: We conducted a retrospective review of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) at our institution. The inclusion criteria involved patients with a naïve major duodenal papilla who required TPS due to difficult biliary cannulation. Papilla morphology was classified using Haraldsson's system, as follows: regular (Type 1), small (Type 2), protruding or pendulous (Type 3), and creased or ridged (Type 4). The analysis focused on identifying risk factors for TPS failure and related complications. Results: A total of 103 cases were analyzed, with an overall TPS success rate of 85.44%. There were no significant differences in age, gender, ERCP indications, or the prevalence of juxtapupillary diverticula across the four papilla types. The TPS failure rates by papilla type were Type 1 (10.53%), Type 2 (0%), Type 3 (16.67%), and Type 4 (28%). Type 4 papilla had a significantly higher failure rate compared to Type 1 and Type 2 in the univariate analysis (p = 0.028), but this was not statistically significant in the multivariate analysis (p = 0.052). Age emerged as an independent risk factor for TPS failure. Conclusions: Duodenal papilla morphology may influence the success rate of TPS, with advanced age being a key risk factor for failure. Identifying high-risk factors such as Type 4 papilla and older age can help endoscopists adjust their techniques early, potentially improving outcomes and minimizing complications.

BackgroundPrecut over a pancreatic duct stent (PPDS) and transpancreatic precut sphincterotomy (TPS) with immediate pancreatic duct stent placement are techniques employed to promote biliary access during endoscopic retrograde cholangiopancreatography (ERCP) in cases of challenging biliary cannulation. However, limited data are available to compare the efficacy of these two pancreatic stent-assisted precut sphincterotomy techniques.AimsThe aim of this study was to compare the efficacy of PPDS versus TPS.MethodsA retrospective analysis was performed on the clinical data of consecutive patients who underwent ERCP between April 1, 2019 and May 31, 2023. According to the selected cannulation approaches, patients were assigned to two groups. In the PPDS group, a pancreatic duct stent was initially placed, followed by needle-knife precut over the stent. In the TPS group, transpancreatic precut sphincterotomy was initially performed, followed by immediate pancreatic stent placement. The success rate of biliary cannulation and the incidence of post-ERCP pancreatitis (PEP) between the two groups were analysed.ResultsAmong 864 patients who underwent ERCP, 46 patients were equally enrolled in the two groups. Selective bile duct cannulation was successfully achieved in 42 out of 46 (91.3%) cases using the PPDS and in 32 out of 46 (69.6%) cases using TPS technique alone, indicating significantly higher success rate of bile duct cannulation with PPDS compared to TPS (91.3% vs. 69.6%, P = 0.009). The overall success rates for bile duct cannulation were 93.5% and 97.8% in the PPDS and TPS groups, respectively, with no significant difference identified (P = 0.307). PEP occurred in 0 and 4 (8.7%) cases in the PPDS and TPS groups, respectively, with no significant difference between the two groups (8.7% vs. 0%, P = 0.117). There were no cases of bleeding or perforation in either group.ConclusionsBoth PPDS and TPS followed by immediate pancreatic duct stent placement are viable options. TPS stands out for its simplicity and cost-effectiveness, while PPDS is more appropriate for patients who are at a high-risk of developing PEP.

Introduction The role of ERCP to diagnose and manage biliopancreatic diseases is increasing since its inception with refinement of operator skill, technical advancement and better patient selection. The aim of the study was to explore common clinical and endoscopic characteristics, outcome, adverse events and safety profile of patients. MethodsAn observational study was conducted on patients undergoing ERCP in Department of Gastroenterology, Tribhuvan University Teaching Hospital, for management of biliopancreatic diseases from April 2023 to March 2024 after taking approval from IRC-IOM. Patient demographics, clinical characteristics, ERCP findings and post procedure outcome data were collected and analyzed using SPSS version 26. ResultsA total of 200 patients were included with mean age 52.36±17.04 years and female:male ratio of ~3:2. Elective procedures were done in 182 (91%) patients and in 18 (9%) as urgent procedure (within 48 hours). The most common indications were choledocholithiasis (157, 78.5%) followed by benign biliary stricture (12, 6%). The most frequent papilla was type 1 papilla (normal variant) in 48% followed by type 3 papilla (protruding) in 30%. Difficult cannulation was encountered in 130 (51.5%) cases. Post ERCP pancreatitis (8, 4%) and hypoxia (9, 4.5%) were the most common procedure and anesthesia related adverse events respectively. Common therapeutic interventions included sphincterotomy (176, 88%), CBD stenting (154, 78.5%) and precut sphincterotomy (45, 22.5%). ConclusionERCP was mostly done for benign diseases like CBD stone and benign biliary strictures. Common therapeutic procedures were sphincterotomy and CBD stenting. Complications related to procedure and anesthesia though occured, their rate was low.

The standard salvage technique used for difficult bile duct cannulation is precut sphincterotomy, whereas endoscopic ultrasound-guided rendezvous technique (EUS-RV) is a relatively newer method. Prospective comparative data between these 2 techniques as salvage for biliary access in patients with benign biliary disease and difficult bile duct cannulation is lacking. To compare EUS-RV and precut sphincterotomy as salvage technique for difficult bile duct cannulation in benign biliary obstruction. Participant-masked, parallel-group, superiority, randomized controlled trial. (Clinical Trials Registry of India: CTRI/2020/07/026613). Tertiary care academic institute from July 2020 to May 2021. All patients with benign biliary disease and difficult bile duct cannulation requiring salvage strategy. Patients were randomly assigned by computer-generated randomized blocks sequence in 1:1 fashion to either EUS-RV or precut sphincterotomy. Patients with failure in EUS-RV were crossed over to precut sphincterotomy and vice versa. The primary outcome measure was technical success. The other outcome measures included procedure time, radiation dose, and adverse events. In total, 100 patients were randomly assigned to EUS-RV (n = 50) and precut sphincterotomy (n = 50). The technical success rate (92% vs. 90%; P = 1.00; relative risk, 1.02 [95% CI, 0.90 to 1.16]), median procedure time (10.1 vs. 9.75 minutes), and overall complication rate (12% vs. 10%; relative risk, 1.20 [CI, 0.39 to 3.68]) were similar between the 2 groups. Five patients (10%) in the EUS-RV group and 5 patients (10%) in the precut sphincterotomy group had developed post-endoscopic retrograde cholangiopancreatography pancreatitis. All failed cases in either salvage group could be successfully cannulated when crossed over to the other group. Single center study done by experts. Endoscopic ultrasound-guided rendezvous technique and precut sphincterotomy have similar success rates as salvage techniques in the technically challenging cohort of difficult bile duct cannulation for benign biliary disease, with acceptable complications rates. None.

Background and Aim: Endoscopic retrograde cholangiopancreatography (ERCP) is a valuable procedure for pancreatobiliary disorders but carries significant risks, including post-ERCP pancreatitis (PEP). The exact cause of PEP is unclear, but mechanical and thermal injuries during the procedure and patient-related factors have been implicated. This study aims to investigate the possible contribution of potential pancreatotoxic drug (PPD) exposure to PEP risk. Methods: This was a retrospective, single-centre, cohort study conducted at Canberra Hospital, a tertiary university hospital. Consecutive ERCP performed with native papillae within a 4-year period from January 2019 to January 2023 were evaluated. Details of ERCP procedures, patient characteristics, and all medications were contemporaneously collected. All patients had follow-up phone calls or review within 24 h post procedure. The diagnosis of PEP was based on the Cotton consensus definition. Results: A total of 32 out of 444 patients (7.2%) developed PEP. There was no significant difference in the incidence of PEP between patients taking PPD compared to patients who were not (7.1% vs. 7.6%, p = 0.845). Three factors were independently associated with PEP in the multivariate analysis: the presence of a periampullary diverticulum (OR = 5.4, 95% CI 1.7–15.3, p = 0.002), the performance of pre-cut sphincterotomy (OR = 2.8, 95% CI 1.2–6.4, p = 0.017), and pancreatic duct cannulation (OR = 3, CI 1.3–7, p = 0.01). Conclusions: The overall incidence of pancreatitis in our selected group of ERCP patients with native papillae was 7.2%. Our study did not find the use of PPD to be a statistically significant risk factor for PEP.

Abstract Introduction Difficult biliary cannulation leads to prolonged papillary manipulation and repeated attempts at cannulation are known to increase the risk of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. This study aims to compare the efficacy and complications of three rescue methods, transpancreatic biliary sphincterotomy (TP), double guidewire technique (DGW), and precut sphincterotomy (precut) in difficult common bile duct (CBD) cannulations. Methods Seventy-six patients (&gt;12 years of age) with a native papilla undergoing ERCP for biliary cannulation were recruited. Those who had inadvertent pancreatic duct cannulations (&gt;1) were included. A pancreatic stent was inserted in all cases. They underwent either DGW (n = 25), precut (n = 25), or TP (n = 26) as rescue methods and were compared in terms of the success of cannulation and post-ERCP complications. Results Of the total 76 cases, 82% were for benign indications, the most common being choledocholithiasis (69.7%). Jaundice was noted in 52% (n = 13/25), 60% (n = 15/25), and 38.5% (n = 10/26) of the DGW, precut, and TP cases, while 40% (n = 10/25), 12% (n = 3/25), and 30.8% (n = 8/26), respectively, were in cholangitis at presentation. The most common type of papilla was type 1 overall and each subgroup. While successful cannulation was achieved in 88.5% (n = 23/26) of TP and 84% (n = 21/25) of the DGW group, only 64% (n = 16/25) of the precut cases were cannulated. Three (n = 3/25) cases had mild bleeding and two mild pancreatitis, one severe pancreatitis, and one perforation were recorded in the precut group. One patient each had severe and mild pancreatitis in the DGW group, while one had mild pancreatitis and two had moderate pancreatitis in the TP group. All the patients were managed conservatively. Conclusion There was no significant difference in the technical success rate (p = 0.075) as well as complications (p = 0.117) between the three salvage methods for difficult naive CBD cannulations.

Clinically significant post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding (CSPEB) is common. Contemporary estimates of risk are lacking. We aimed to identify risk factors of and outcomes after CSPEB. We analyzed multicenter prospective ERCP data between 2018 and 2024 with 30-day follow-up. The primary outcome was CSPEB, defined as hematemesis, melena, or hematochezia resulting in (i) hemoglobin drop ≥ 20 g/L or transfusion and/or (ii) endoscopy to evaluate suspected bleeding and/or (iii) unplanned healthcare visitation and/or prolongation of existing admission. Firth logistic regression was used. P values <0.05 were significant, with odds ratios (ORs) and 95% confidence intervals reported. CSPEB occurred after 129 (1.5%) of 8,517 ERCPs (mean onset 3.2 days), with 110 of 4,849 events (2.3%) occurring after higher risk interventions (sphincterotomy, sphincteroplasty, precut sphincterotomy, and/or needle-knife access). Patients with CSPEB required endoscopy and transfusion in 86.0% and 53.5% of cases, respectively, with 3 cases (2.3%) being fatal. P2Y 12 inhibitors were held for a median of 4 days (interquartile range 4) before higher risk ERCP. After higher risk interventions, P2Y 12 inhibitors (OR 3.33, 1.26-7.74), warfarin (OR 8.54, 3.32-19.81), dabigatran (OR 13.40, 2.06-59.96), rivaroxaban (OR 7.42, 3.43-15.24), and apixaban (OR 4.16, 1.99-8.20) were associated with CSPEB. Significant intraprocedural bleeding after sphincterotomy (OR 2.32, 1.06-4.60), but not after sphincteroplasty, was also associated. Concomitant cardiorespiratory events occurred more frequently within 30 days after CSPEB (OR 12.71, 4.75-32.54). Risks of antiplatelet-related CSPEB may be underestimated by endoscopists based on observations of suboptimal holding before higher risk ERCP. Appropriate periprocedural antithrombotic management is essential and could represent novel quality initiative targets.