Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an alternative to surgery for acute cholecystitis (AC) in poor operative candidates. However, the role of EUS-GBD in non-cholecystitis (NC) indications has not been well studied. We compared the clinical outcomes of EUS-GBD for AC and NC indications. Consecutive patients undergoing EUS-GBD for all indications at a single center were retrospectively analyzed. Fifty-one patients underwent EUS-GBD during the study period. Thirty-nine (76%) patients had AC while 12 (24%) had NC indications. NC indications included malignant biliary obstruction (n= 8), symptomatic cholelithiasis (n= 1), gallstone pancreatitis (n= 1), choledocholithiasis (n= 1), and Mirizzi’s syndrome (n= 1). Technical success was noted in 92% (36/39) for AC and 92% (11/12) for NC (p> 0.99). The clinical success rate was 94% and 100%, respectively (p> 0.99). There were four adverse events in the AC group and 3 in the NC group (p= 0.33). Procedure duration (median 43 vs. 45 min,p= 0.37), post-procedure length of stay (median 3 vs. 3 days,p= 0.97), and total gallbladder-related procedures (median 2 vs. 2,p= 0.59) were similar. EUS-GBD for NC indications is similarly safe and effective as EUS-GBD in AC.