The mortality associated with acute acalculous cholecystitis approaches 50%. Removal or decompression of the gallbladder in these patients may prevent gallbladder rupture and may be lifesaving. This is usually accomplished by cholecystectomy, cholecystotomy, or percutaneous gallbladder drainage. We describe a novel transpapillary endoscopic approach to gallbladder drainage in patients at high surgical risk. A total of seven high surgical risk patients were treated with transpapillary endoscopic cholecystotomy. Cannulation of the cystic duct was accomplished by using standard hourglass-tipped catheters in two patients. A new ''selector'' catheter was developed for selective cannulation of the cystic duct and used in the other five patients. Five of the seven patients showed evidence of clinical, radiographic and laboratory improvement after treatment. We conclude that transpapillary endoscopic cholecystotomy may be an effective treatment alternative for high surgical risk patients with acalculous cholecystitis.