Occasionally, cholecystectomy is not possible because the patient is not suitable for surgery, and non-operative management should be performed. In these patients, the non-operative management can be through the percutaneous transhepatic gallbladder drainage (PTGBD) or the endoscopic gallbladder drainage. We decided to compare the efficacy and safety of PTGBD and EUS-GBD in the non-operative management of patients with acute cholecystitis. We conducted a systematic review in different databases, such as PubMed, OVID, Medline, and Cochrane Databases. This meta-analysis considers studies published until September 2021. Six studies were selected (2 RCTs). These studies included 749 patients. The mean age was 72.81 ±7.41 years, and males represented 57.4%. EUS-GBD technical success was lower than PTGBD (RR, 0.97; 95% CI, 0.95-0.99), whereas clinical success and adverse events rates were sim...