The efficacy and occurrence of adverse effects after two forms of treatment were compared in 111 patients with biliary colic and radiolucent gallstones in this prospective, nonrandomized study. Fifty-four patients received extracorporeal shock-wave lithotripsy (ESL) plus ursodiol, and 57 patients received ursodiol alone. Among patients with a single stone (5-20 mm in size), no patient treated with ursodiol alone had a stone-free gallbladder at 6 or 12 months after treatment; of those treated with ESL plus ursodiol, 15 of 24 patients (63%) had a stone-free gallbladder at 6 months and 17 of 20 patients (85%) at 12 months. For patients with multiple stones (with an aggregate diameter of less than or equal to 30 mm), the incidence of a stone-free gallbladder was 2 of 43 patients (5%) at 6 months and 8 of 35 patients (23%) at 12 months in the ursodiol treatment group. In the ESL plus ursodiol group, the incidence of a stone-free gallbladder was 7 of 22 patients (32%) at 6 months and 9 of 20 patients (45%) at 12 months. Two patients in the ESL plus ursodiol group (4%) and 13 patients in the ursodiol group (24%) underwent cholecystectomy. Both patients in the ESL plus ursodiol therapy and 4 patients in the ursodiol group had emergency cholecystectomies because of acute cholecystitis. The remaining 9 patients in the ursodiol group had elective cholecystectomies. In this nonrandomized, prospective study, ESL plus ursodiol treatment produced stone-free gallbladders at a faster rate than ursodiol alone in patients with either single or multiple gallstones.