Background: Endoscopic extraction of bile duct stones after sphincterotomy has a success rate of up to 95%. Failures occur in patients with extremely large stones, intrahepatic stones, and bile duct strictures. This study examined the efficacy and the safety of extracorporeal shock-wave lithotripsy in a large cohort of patients in whom routine endoscopic measures including mechanical lithotripsy had failed to extract bile duct stones. Methods: Out of 1587 consecutive patients, endoscopic stone extraction including mechanical lithotripsy was unsuccessful in 313 (20%). These 313 patients (64% women, median age, 73 years) underwent high-energy extracorporeal shock-wave lithotripsy. Stone targeting was performed fluoroscopically (99%) or by ultrasonography (1%). Results: Complete clearance of bile duct calculi was achieved in 281 (90%) patients. In 80% of the patients, the fragments were extracted endoscopically after shock-wave therapy; spontaneous passage was observed in 10%. For patients with complete clearance compared with those without there were no differences with regard to size or number of the stones, intrahepatic or extrahepatic stone location, presence or absence of bile duct strictures, or type of lithotripter. Cholangitis (n = 4) and acute cholecystitis (n = 1) were the rare adverse effects. Conclusions: In patients with bile duct calculi that are difficult to extract endoscopically, high-energy extracorporeal shock-wave lithotripsy is a safe and effective therapy regardless of stone size, stone location, or the presence of bile duct stricture. (Gastrointest Endosc 2001;53:27-32.)