BACKGROUND Percutaneous transhepatic gallbladder drainage has been the most frequently performed treatment for acute cholecystitis for patients who are not candidates for surgery. Endoscopic transpapillary gallbladder drainage (ETGBD) has evolved into an alternative treatment. There have been numerous retrospective and prospective studies evaluating ETGBD for acute cholecystitis, though results have been variable. AIM To evaluate the efficacy and safety of ETGBD in the treatment of inoperable patients with acute cholecystitis. METHODS We performed a systematic review of major literature databases including PubMed, OVID, Science Direct, Google Scholar (from inception to March 2021) to identify studies reporting technical and clinical success, and post procedure adverse events in ETGBD. Weighted pooled rates were then calculated using fixed effects models for technical and clinical success, and post procedure adverse events, including recurrent cholecystitis. RESULTS We found 21 relevant articles that were then included in the study. In all 1307 patients were identified. The pooled technical success rate was 82.62% [95% confidence interval (CI): 80.63-84.52]. The pooled clinical success rate was found to be 94.87% (95%CI: 93.54-96.05). The pooled overall complication rate was 8.83% (95%CI: 7.42-10.34). Pooled rates of post procedure adverse events were bleeding 1.03% (95%CI: 0.58-1.62), perforation 0.78% (95%CI: 0.39-1.29), peritonitis/bile leak 0.45% (95%CI: 0.17-0.87), and pancreatitis 1.98% (95%CI: 1.33-2.76). The pooled rates of stent occlusion and migration were 0.39% (95%CI: 0.13-0.78) and 1.3% (95%CI: 0.75-1.99) respectively. The pooled rate of cholecystitis recurrence following ETGBD was 1.48% (95%CI: 0.92-2.16). CONCLUSION Our meta-analysis suggests that ETGBD is a feasible and efficacious treatment for inoperable patients with acute cholecystitis.