To compare the efficiency (stone fragmentation and removal time) and complications of three models of intracorporeal lithotripters in percutaneous nephrolithotomy (PCNL). Prospective, randomized controlled trial at nine centers in North America from 2009 to 2016. Patients were randomized to one of three lithotripter devices: the Cyberwand, a dual-probe ultrasonic device; the Swiss Lithoclast Select, a combination pneumatic and ultrasonic device; and the StoneBreaker, a portable pneumatic device powered by CO2 cartridges. Since the StoneBreaker lacks an ultrasonic component, it was used with the LUS-II ultrasonic lithotripter to allow fair comparison with combination devices. Two hundred seventy patients were enrolled, 69 were excluded after randomization. Two hundred one patients completed the study: 71 in the Cyberwand group, 66 in the Lithoclast Select group, and 64 in the StoneBreaker group. The baseline patient characteristics of the three groups were similar. Mean stone surface area was smaller in the StoneBreaker group at 407.8 mm2 vs 577.5 mm2 (Lithoclast Select) and 627.9 mm2 (Cyberwand). The stone clearance rate was slowest in the StoneBreaker group at 24.0 mm2/min vs 28.9 mm2/min and 32.3 mm2/min in the Lithoclast Select and Cyberwand groups, respectively. After statistically adjusting for the smaller mean stone in the StoneBreaker group, there was no difference in the stone clearance rate among the three groups (p = 0.249). Secondary outcomes, including complications and stone-free rates, were similar between the groups. The Cyberwand, Lithoclast Select, and the StoneBreaker lithotripters have similar adjusted stone clearance rates in PCNL for stones >2 cm. The safety and efficacy of these devices are comparable.