<jats:sec><jats:title>Objectives</jats:title><jats:p>Patients with acute cholecystitis receiving antithrombotic therapy (ATT) have an increased risk of bleeding complications during surgery and percutaneous drainage. Endoscopic transpapillary gallbladder drainage (ETGBD) is recommended for such cases; however, evidence is limited. To investigate this issue further, we performed a retrospective multicenter study.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>One hundred thirty patients with acute cholecystitis who underwent ETGBD were enrolled. They were divided into an ATT group (continuation of ATT on the day of the procedure and/or heparin substitution) and a Non‐ATT group (discontinuation or no use of ATT). The primary outcome was bleeding complication rate, and the secondary outcomes were technical success rate, clinical success rate and total complication rate.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Eighty‐three patients were enrolled in the ATT group, and 47 were enrolled in the Non‐ATT group. In the ATT group, 42.2% continued multi‐agent ATT. No bleeding complications occurred in either group. There were no significant differences between the ATT and Non‐ATT groups in the technical success rate (84.3% vs 89.4%, <jats:italic>P</jats:italic> = 0.426 respectively) or the clinical success rate (97.1% vs 100%, <jats:italic>P </jats:italic>= 0.259, respectively). The overall early complication rate was 3.1% (4/130): mild pancreatitis (<jats:italic>n</jats:italic> = 3) and cholangitis (<jats:italic>n</jats:italic> = 1). Stent dysfunction was found in 10.9% of patients (at 196 days on average), and the 12‐month stent patency rate was 69.0%.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>No significant difference was found in the bleeding complication rate between ETGBD with and without ATT. ETGBD may be an ideal drainage method for patients with acute cholecystitis receiving ATT.</jats:p></jats:sec>