The use of bile acid dissolution therapy in extracorporeal shockwave lithotripsy of gallstones, remains controversial. Our study examined whether chemolitholysis after sufficient disintegration enhanced stone clearance within 6 months of the first lithotripsy. A total of 143 patients who developed one to three radiolucent stones measuring < or = 30 mm in diameter were randomly separated into two treatment groups: 47% were given lithotripsy alone, and 53% lithotripsy plus ursodeoxycholic acid (UDCA). Repeated piezoelectric lithotripsy was given, with no limit on the total number of treatment sessions, to pulverize or disintegrate stones into fragments < 3 mm. Stones were disintegrated in 97% of all patients, and the fragments were < or = 2 mm in 50% of these patients. According to an intention-to-treat analysis, 52% in the lithotripsy alone group and 58% in the UDCA group were free of stones 6 months after the first lithotripsy (P = 0.61). Of the patients with fragments < or = 2 mm, 71% in the former and 86% in the latter group were free of stones 6 months after the first lithotripsy, with no significant difference between the groups. Biliary pain occurred in 25% of all patients, including 3 with acute cholecystitis. We concluded that the sufficient disintegration of gallstones achieved with repeated lithotripsy enhanced the early clearance of fragments, regardless of whether chemolitholysis was employed.