Objectives: To evaluate the durability of 4 next-generation flexible ureteroscopes in a randomized, multi-institutional, prospective study. Methods: Patients at 3 institutions were randomized to 1 of 4 flexible ureteroscopes: the Wolf Viper, Olympus URF-P5, Gyrus-ACMI DUR-8 Elite (DUR-8E), and Stryker FlexVision U-500. Each center used 1 scope from each manufacturer until it needed major repair (primary endpoint). Intraoperative data included total time of use, number of scope insertions through an access sheath, working time in the lower pole, number of insertions and total time for accessory instrumentation in the working channel, number of laser insertions through the working channel, and total laser energy used. Results: A total of 175 patients were randomized. The DUR-8E experienced early catastrophic failure (≤ 10 cases) at all 3 sites; however, this also occurred at 1 site each for the Stryker and Wolf scopes. The DUR-8E required major repair after the fewest average number of cases (5.3), the lowest average total time of usage (108 minutes), the fewest insertions through an access sheath (20.3), the shortest duration of laser firing (31.3 minutes), and the shortest instrument in the working channel time (224.7 minutes). As such, due to variation in durability within manufacturers, no differences could be demonstrated. Visibility ratings for the Wolf iper were significantly better than the DUR-8E (P = .034) and the Flexvision (P = .038). Conclusions: The Wolf Viper, Olympus URF-P5, and Stryker Flexvision U-500 flexible ureteroscopes seem comparable with regard to durability. However, larger prospective registry-based studies are needed to document significant differences between them.