EUS-guided gallbladder drainage (EUS-GBD) with LAMS is increasingly used in managment of acute cholecystitis (AC) in patients unfit for surgery or with malignant distal biliary obstruction. Evidence comparing the trans-gastric (TG) and trans-duodenal (TD) routes remains limited.

This international, multicenter retrospective study included all consecutive patients undergoing EUS-GBD from January 2019 to August 2025 across five tertiary centers (Italy, France, India). Standardized data collection included baseline characteristics, procedural variables, technical success (TS), clinical success (CS), adverse events (AEs; AGREE classification), recurrence, and recurrence-free survival (Kaplan–Meier). TS was defined as successful LAMS deployment; CS as resolution of the index condition without further intervention. Recurrence was defined as symptomatic or infectious relapse requiring reintervention.

A total of 194 patients were included (84 TG; 110 TD). Indications were acute cholecystitis in 69.6% and malignant biliary drainage in 30.4%. Overall TS and CS were 98.5% and 96.9%, respectively, with 5.9% recurrence. TS was comparable between groups (TG 98.8% vs TD 98.2%; P=0.726). However, CS was significantly lower in the TG group (92.8% vs 100% in TD; P=0.0046). Procedural time was also significantly longer in TG (17 vs 10 minutes; P=0.0073). Hospital stay did not differ (6 vs 6 days; P=0.385). Overall AEs were similar (19.0% vs 14.5%; P=0.404), but LAMS obstruction occurred significantly more frequently in TG (8.3% vs 1.8%; P=0.033). Other AEs — LAMS migration (1.2% vs 0.9%; P=0.866), bleeding (2.4% vs 2.7%; P=0.907), and cholangitis (5.9% vs 5.4%; P=0.882) —did not differ significantly. Recurrence remained similar (5.2% vs 6.5%; P=0.716). Kaplan–Meier analysis confirmed no difference in recurrence-free survival between TG and TD (log-rank P=0.986).

EUS-GBD is highly feasible, effective, and safe across international real-world settings. The transduodenal approach demonstrated significantly higher clinical success and significantly shorter procedure time, while safety and recurrence outcomes were comparable. When anatomically possible, TD drainage may represent the preferred route.