INTRODUCTION: Cholecystectomy is the treatment of choice for patients with acute cholecystitis (AC). In high-risk non-surgical patients with many comorbidities, endoscopic ultrasound-guided gallbladder drainage (EUS-GB) via a lumen-apposing metal stent (LAMS), percutaneous cholecystostomy (PC), and endoscopic transpapillary cystic duct stenting (CDS) are alternatives to surgical management. However, data comparing the three modalities is limited. Our aim was to study outcomes of EUS-GB vs PC vs CDS in non-surgical patients with AC. METHODS: We retrospectively analyzed data for patients with AC between 2016 and 2020. Diagnosis was established using ICD-9 and ICD-10 codes. Patients with prior cholecystectomy, age < 18 years, and those without routine follow-up were excluded. Outcomes included total fluoroscopy time, post-procedural pain, narcotic use, clinical success, reinterventions, adverse events (AE), hospital length of stay (LOS), and mortality. Characteristics and outcomes were compared using one-way ANOVA or Kruskal-Wallis tests for continuous variable and Pearson’s chi-square or Fisher’s exact tests for categorical variables. Logistic regression models were used to estimate odds ratios and 95% confidence intervals. RESULTS: A total of 5323 patients with AC were reviewed, of which 182 non-surgical patients met our inclusion criteria (Figure 1). Mean age was 76.5 years and 61.2% were males, with 55 patients who underwent EUS-GB, 105 PC, and 23 CDS (Table 1). Baseline characteristics between the groups were similar. Total fluoroscopy time was significantly lower in the EUS-GB patients (1.7 mins) vs PC (3 mins) and CDS (3.9 mins) (P = 0.0002). Post-procedural pain and narcotic use were significantly lower in the EUS-GB and CDS patients compared to PC (P < 0.0001) (Table 2). Patients with EUS-GB and CDS (0% & 17.4%) underwent significantly fewer reinterventions compared to PC (92.4%, P < 0.0001). The EUS-GB (3.6%) and CDS (13%) group had significantly lower AE compared to PC (61%, P < 0.0001). The LOS was significantly lower in EUS-GB and CDS patients vs PC (P = 0.0027). Mortality between all the groups was similar. CONCLUSION: In high-risk non-surgical patients with AC, EUS-GB via LAMS is safer and more effective compared to CDS and PC as it is associated with the significantly shorter fluoroscopy time, less post-procedural pain and narcotic use, fewer AE, and the least recurrence of cholecystitis.Figure 1.: Inclusion and exclusion criteria for final analysis.Table 1.: Outcomes for EUS-GB vs PC vs CDS patientsTable 2.: Odds ratio for developing post-procedural pain and subsequent narcotic use