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Introduction and Objective: Current available lithotrites have clinical stone clearance rates averaging 24 to 32 mm2/minute. The objective of this study was to critically evaluate the initial experience with the Swiss LithoClast® Trilogy lithotrite during percutaneous nephrolithotomy (PCNL). Methods: We prospectively enrolled patients with a minimum of 15 mm of stone in axial diameter at three locations (Indiana University, University of California Davis, and University of California San Diego) scheduled to undergo PCNL for nephrolithiasis over a 60-day trial period. We assessed objective measures of stone clearance time, stone clearance rate, device malfunction, stone-free rate, and complications. Each surgeon also evaluated subjective parameters from each case related to the use of Trilogy on a 1 to 10 scale (10 = extremely effective), and compared it with their usual lithotrite on a 1 to 5 scale (5 = much better). Results: We included 43 patients and had 7 bilateral (16.3%) cases, for a total of 50 renal units. One case was a mini-PCNL. Two cases experienced device malfunctions requiring troubleshooting but no transition to another lithotrite. The mean stone clearance rate was 68.9 mm2/minute. The stone-free rate on postoperative imaging was 67.6% (25 of 37 patients with available imaging). The lowest subjective rating was the ergonomic score of 6.7, and the highest subjective rating was the ease of managing settings score of 9.2. The surgeon impressions of ultrasound (7.3), ballistics (8.1), combination of ultrasound and ballistics (8.7), and suction (8.4) were high. One patient experienced an intraoperative renal pelvis perforation, one patient required a blood transfusion, one patient had a pneumothorax requiring chest tube placement, and one patient had a renal artery pseudoaneurysm requiring endovascular embolization. Conclusions: This multi-institutional study evaluated a new and efficient combination lithotrite that was perceived by surgeons to be highly satisfactory, with an excellent safety and durability profile. [ABSTRACT FROM AUTHOR]