BACKGROUND There are currently no prospective, controlled trials of endoscopic transpapillary gallbladder drainage in patients with acute cholecystitis. OBJECTIVE We evaluated the technical success rate and efficacy of endoscopic transpapillary gallbladder drainage by using either endoscopic nasogallbladder drainage (ENGBD) or endoscopic gallbladder stenting (EGBS) for patients with acute cholecystitis. DESIGN Randomized, controlled study. SETTING Tertiary-care referral centers. PATIENTS Seventy-three consecutive patients with acute cholecystitis were randomized. INTERVENTIONS ENGBD by using a 5F or 7F tube (n = 37) or EGBS (n = 36) by using a 7F stent. MAIN OUTCOME AND MEASUREMENTS Technical success, clinical success, adverse events, and procedure-related pain score. RESULTS The overall technical success rates in the ENGBD and EGBS groups were 91.9% and 86.1%, respectively (P > .05). The mean procedure times of ENGBD and EGBS were 20.3 ± 12.1 and 22.2 ± 14.5 minutes, respectively (P > .05). The overall clinical success rates by per protocol analysis were 94.1% and 90.3% in the ENGBD and EGBS groups, respectively, whereas the rates by intention-to-treat analysis were 86.5% and 77.8%, respectively (P > .05). Moderate adverse events were observed in the ENGBD (n = 2) and EGBS (n = 1) groups. The mean visual analog score of postprocedure pain in the ENGBD group was significantly higher than that in the EGBS group (1.3 ± 1.1 vs 0.4 ± 0.8, respectively; P < .001). LIMITATIONS Small sample size and the participation of multiple endoscopists who may have different levels of experience in endoscopic transpapillary gallbladder drainage. CONCLUSIONS Both ENGBD and EGBS appear to be suitable for the treatment of acute cholecystitis in patients who are poor candidates for emergency cholecystectomy. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN000012316.).