The aim of this prospective, randomized study was to compare two second-generation lithotripters based on different physical principles in patients with gallbladder stones at a single lithotripsy center under the same clinical conditions. Sixty patients with one to three symptomatic gallbladder stones were selected for lithotripsy, either with an electrohydraulic or a piezoelectric device. With both lithotripters, treatment was performed under standard conditions (prone position, sonographic monitoring, sedoanalgesia if necessary, up to 3000 pulses/session, retreatments (maximum, two) if fragments > 4 mm, concomitant oral chemolitholysis). If no fragmentation could be obtained in the first session, the other lithotripter was used for the following treatments. The two groups did not differ significantly with regard to the anthropometric data or number and size of stones. In contrast to piezoelectric lithotripsy (0%), with the electrohydraulic lithotripter, iv analgesics and sedatives were necessary in all treatments (100%); however, in 11/53 treatments (21%), patients did not tolerate the full session despite maximum medication. The treatment time was nearly twice as long with electrohydraulic (56 +/- 22 min) than with piezoelectric lithotripsy (31 +/- 8 min) (p < 0.001). With the electrohydraulic lithotripter, used in 20% of the patients, no fragmentation was seen after the first session, and therapeutically adequate fragmentation (< or = 4 mm) occurred in only 33%. In contrast, with the piezoelectric lithotripter, the stones were disintegrated in all patients (p < 0.05); in 50% a maximum fragment size < or = 4 mm was measured after the first treatment. Whereas in the first months after lithotripsy, stone-free rates were higher with piezoelectric lithotripsy (43% vs. 25% after 1 month; 47% vs. 38% after 2 months; 60% vs. 48% after 4 months; NS), rates of complete stone disappearance were equally high in both groups after 12 months (82%).