The Siemens Lithostar Plus protocol (Siemens Medical Systems, Iselin, NJ) allows investigators to perform gallstone lithotripsy on patients regardless of the number of stones they have, provided the stones occupy less than 50% of the gallbladder lumen. The purpose of this study was to determine the interrelationships between stone burden, fragmentation response, and stone-free rates when treatment is not limited to three stones or fewer. Of 200 patients initially examined, 80 (40%) underwent lithotripsy. The mean number of treatments per patient was 2.1, and the mean number of shock waves per patient was 7386. In 60 patients in whom 6-month follow-up was available, the overall stone-free rate, based on actual results, was 32% (19/60). The stone-free rates for solitary stones, two or three stones, and four or more stones were 50%, 12%, and 26%, respectively. Regardless of number of stones, patients who ultimately became stone free had significantly smaller mean fragment size (0.25 cm) 2 weeks after lithotripsy than did those who did not become stone free (0.51 cm). Retrospective volume analysis showed that seven (47%) of 15 patients with multiple stones occupying less than 2000 mm3 were stone free; none became stone free when this volume was exceeded. Lithotripsy remains a practical option for patients with solitary stones. Comparable stone-free rates to those achieved for solitary stones can be obtained in patients with multiple stones, regardless of their number, provided treatment is aggressive and the stone aggregate is less than 2000 mm3.