The effect of ursodiol on the efficacy and safety of extracorporeal shock-wave lithotripsy of gallstones. The Dornier National Biliary Lithotripsy Study BACKGROUND. In the treatment of gallstones with extracorporeal shock-wave lithotripsy, the bile acid ursodiol is administered to dissolve the gallstone fragments. We designed our study to determine the value of administering this agent. METHODS. At 10 centers, 600 symptomatic patients with three or fewer radiolucent gallstones 5 to 30 mm in diameter, as visualized by oral cholecystography, were randomly assigned to receive ursodiol or placebo for six months, starting one week before lithotripsy. RESULTS. The stones were fragmented in 97 percent of all patients, and the fragments were less than or equal to 5 mm in diameter in 46.8 percent. On the basis of an intention-to-treat analysis of all 600 patients, 21 percent receiving ursodiol and 9 percent receiving placebo (P less than 0.0001) had gallbladders that were free of stones after six months. Among those with completely radiolucent solitary stones less than 20 mm in diameter, 35 percent of the patients receiving ursodiol and 18 percent of those receiving placebo (P less than 0.001) were free of stones after six months. Biliary pain, usually mild, occurred in 73 percent of all patients but in only 13 percent of those who were free of stones after three and six months (P less than 0.01). There were few adverse events. Only diarrhea occurred with a significantly different frequency in the two groups: 32.6 percent were affected in the ursodiol group, as compared with 24.7 percent in the placebo group (P less than 0.04). Severe biliary pain occurred in 1.5 percent of all patients, acute cholecystitis in 1.0 percent, and acute pancreatitis in 1.5 percent; endoscopic sphincterotomy was performed in 0.5 percent, and cholecystectomy in 2.5 percent. CONCLUSIONS. Extracorporeal shock-wave lithotripsy with ursodiol was more effective than lithotripsy alone for the treatment of symptomatic gallstones, and equally safe. Treatment was more effective for solitary than multiple stones, radiolucent than slightly calcified stones, and smaller than larger stones. 