Horseshoe kidney (HSK) is one of the most frequent renal malformations which appears to present an increased risk of stone formation caused by abnormal urine drainage. This study aims to compare the results of single-use flexible ureteroscopy (SUfURS) vs reusable devices (RfURS) with holmium laser in treating stones in HSK cases. Between February 2017 and June 2021, 29 patients diagnosed with renal stone disease and horseshoe kidney were retrospectively analyzed. Subjects were divided into two groups: Group 1 (14 patients) undergoing SUfURS and Group 2 (15 patients) operated with RfURS devices. We analyzed the mean stone burden, operation time, stone free rate and complications. The surgical equipment was represented by the SUfURS PU3022 (Zhuhai Pusen Medical Technology) and RfURS URF-V2 (Olympus). The two groups had a similar mean stone burden: 22 ± 6 mm (range 15-31 mm) for Group 1 and 24 ± 7 mm (range 16-30 mm) for Group 2. The average operative time was better for Group 1 (86 ± 17 min) vs Group 2 (89 ± 20 min). The stone-free status was similar for both groups after the first session (57.14% for Group 1 vs 53.33% for Group 2) and slightly in favor of Group 1 as compared to Group 2 (85.71% vs 73.33%, respectively) after the second session. The overall complication rate (Grades I, II and III) was almost similar in both groups, with a slightly prevalence for Group 1 (no major complications Grade IV and V). Flexible ureteroscopy represents an effective alternative treatment technique for large stones in kidney abnormalities. single-use flexible ureteroscopy can be successfully used to treat patients with genetically renal malformations and its results may be slightly better than those provided by using RfURS devices.