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Introduction: The aim of this study was to assess the feasibility of sparing routine antibiotic prophylaxis in patients without preoperative urinary tract infection undergoing ureterorenoscopy (URS) for stone removal., Methods: A retrospective, monocentric study was conducted to evaluate the outcome of a modified perioperative antibiotic management strategy according to the principles of antibiotic stewardship. Patients with preoperative unremarkable urine culture received no antibiotic prophylaxis for URS stone removal (NoPAP). The NoPAP group was compared to a historic URS cohort, when antibiotic prophylaxis (PAP) was standard of care. Analysis focused on postoperative complications., Results: Postoperative fever occurred in 1% of the NoPAP and 2% of the PAP patients (p = 0.589). Clavien 1-3 complications did not differ between groups with 9% in the NoPAP and 6.2% in the PAP (p = 0.159). No Clavien 4-5 complications were seen. We identified a residual stone (p = 0.033) and an ASA score 3-4 (p = 0.004) as significant risk factors for postoperative fever. By sparing routine antibiotic prophylaxis, the overall antibiotic usage was reduced from 100% (PAP) to 8.3% (NoPAP)., Conclusion: Sparing a routine antibiotic prophylaxis during URS for stone removal seems feasible in patients with unremarkable preoperative urine culture for most of the patients. A prospective validation is warranted., (© 2024 The Author(s). Published by S. Karger AG, Basel.)