To conduct a comparative evaluation of ultrasonic, pneumatic, and dual ultrasonic (DUS) lithotripsy to predict the safety of probes on urinary tract tissue.The Swiss Lithoclast Ultra (ultrasonic-only [US] and ultrasonic-pneumatic combination [US+P]) and the Gyrus ACMI Cyberwand (DUS) were evaluated. Fresh porcine ureter, bladder, and renal pelvis tissues were used with a hands-free setup to vertically apply 0, 400, or 700 g of force with each probe for a duration of 3 seconds, 5 seconds, or 3 minutes (or until perforation occurred). Data collection included whether perforation occurred and time to perforation. Histological analysis of nonperforated samples was used to compare the anatomical depth to which damage occurred.The total percentage of trials resulting in perforation for all tissue types, contact durations, and forces was found to be 8.5% (10/117) for US, 13.7% (16/117) for US+P, and 26.4% (31/117) for DUS. No perforations occurred with light contact (0 g) of probe force, regardless of tissue type, lithotripsy mode, or contact duration. Overall, the renal pelvis was most resistant to perforation (p=0.0004), while no difference was found between the bladder and ureter tissue (p=0.32). Force beyond 400 g and contact greater than 5 seconds increased risk for damage.Mode of lithotripsy, tissue type, probe force, and probe-tissue contact duration all significantly impacted the extent of damage and likelihood for perforation to occur. All devices and tissue types provided a reasonable margin of safety for probe-tissue contact times of 3 and 5 seconds with no more than 400 g of force.