INTRODUCTION: There is a known association of biliary stones with cystic fibrosis (CF). The CFTR expression in the gallbladder is described as one of the highest of all human tissues. Consequently, CFTR activity is imperative in the biliary tree and its absence can lead to significant biliary disease due to decreased secretion of biliary bicarbonate and disturbance of normal bile acid circulation. ERCP has an important role in the diagnosis and management of CF patients. However, there is very limited data evaluating the outcomes and the adverse events (AEs) post ERCP in these patients. Therefore, we conducted this study to evaluate ERCP-related AEs in CF patients using a large national cohort. METHODS: A retrospective cohort study was performed using the National Inpatient Sample (NIS) database 2011–2014. We identified all adult patients (≥18 year old) who underwent ERCP using ICD-9 codes. Primary outcomes comprised ERCP-related AEs including post ERCP pancreatitis (PEP), bleeding and perforation. Secondary outcomes included all-cause mortality (ACM) and length of hospital stay (LOS). Primary and secondary outcomes were compared between the study and control group using multivariate logistic regression analysis. RESULTS: We identified a total of 108,182 patients underwent ERCP, of which 73 (0.07%) had CF. CF patients were younger (31.75 ± 14.5 vs 58.48 ± 20.14), less females (49.7% vs 59.7%) and less likely to be African American (4.3% vs 9.1%) compared to the control group, (P < 0.05 for all. In addition, CF patients had less alcohol (1.4% vs 4.3%, P > 0.05) compared to the control group. Using multivariate logistic regression and after adjusting for potential cofounding factors including age, race, gender and Elixhauser comorbidities, patients with CF had no statistically significant difference in PEP (OR 0.99, 95% CI: 0.31–3.23) or bleeding (OR 3.22, 95% CI: 0.44–23.63). In addition, the control group had 0.04% (n = 48) total cases of post ERCP perforation reported and 1% (n = 1093) of ACM while none were reported in CF patients. Further, the adjusted LOS was slightly longer in the CF group compared to the control group (8.33 ± 6.37 vs 5.49 ± 5.04 day, P < 0.05). CONCLUSION: CF patients undergoing ERCP might have slightly increase in the LOS, however they have comparable outcomes and similar risk of AEs comparing to other patients who don’t carry this diagnosis.