Background and study aims The aim of the current study was to review the outcomes of a large-scale international registry on endoscopic ultrasound-guided gallbladder drainage (EGBD) that encompasses different stent systems in patients who are at high-risk for cholecystectomy. Patients and methods This was a retrospective international multicenter registry on EGBD created by 13 institutions around the world. Consecutive patients who received EGBD for several indications were included. Outcomes include technical and clinical success, unplanned procedural events (UPE), adverse events (AEs), mortality, recurrent cholecystitis and learning curve of the procedure. Results Between June 2011 and November 2017, 379 patients were recruited to the study. Technical and clinical success were achieved in 95.3 % and 90.8 % of the patients, respectively. The 30-day AE rate was 15.3 % and 30-day mortality was 9.2 %. UPEs were significantly more common in patients with EGBD performed for conversion of cholecystostomy and symptomatic gallstones ( P < 0.001); and by endoscopists with experience of fewer than 25 procedures ( P = 0.033). Both presence of clinical failure ( P = 0.014; RR 8.69 95 %CI [1.56 - 48.47]) and endoscopist experience with fewer than 25 procedures ( P = 0.002; RR 4.68 95 %CI [1.79 - 12.26]) were significant predictors of 30-day AEs. Presence of 30-day AEs was a significant predictor of mortality ( P < 0.001; RR 103 95 %CI [11.24 - 944.04]). Conclusion EGBD was associated with high success rates in this large-scale study. EGBD performed for indications other than acute cholecystitis was associated with higher UPEs. The number of cases required to gain competency with the technique by experienced interventional endosonographers was 25 procedures.