ObjectivesThis work aims to determine the efficacy and safety of preoperative alpha‐blocker therapy on ureteroscopy (URS) outcomes.MethodsIn this systematic review and meta‐analysis of randomised trials of URS with or without preoperative alpha‐blocker therapy, outcomes included the need for ureteral dilatation, stone access failure, procedure time, residual stone rate, hospital stay, and complications. Residual stone rates were reported with and without adjustments for spontaneous stone passage, medication noncompliance, or adverse events leading to patient withdrawal. Data were analysed using random‐effects meta‐analysis and meta‐regression. Certainty of evidence was assessed using the GRADE criteria.ResultsAmong 15 randomised trials with 1653 patients, URS was effective and safe with a stone‐free rate of 81.2% and rare (2.3%) serious complications. The addition of preoperative alpha‐blockers reduced the need for ureteral dilatation (risk ratio [RR] = 0.48; 95% CI = 0.30 to 0.75; p = 0.002), access failure rate (RR = 0.36; 95% CI = 0.23 to 0.57; p < 0.001), procedure time (mean difference [MD] = −6 min; 95% CI = −8 to −3; p < 0.001), risk of residual stone in the primary (RR = 0.44; 95% CI = 0.33 to 0.66; p < 0.001) and adjusted (RR = 0.52; 95% CI = 0.40 to 0.68; p < 0.001) analyses, hospital stay (MD = −0.3 days; 95% CI = −0.4 to −0.1; p < 0.001), and complication rate (RR = 0.46; 95% CI = 0.35 to 0.59; p < 0.001). Alpha‐blockers increased ejaculatory dysfunction risk and were less effective for renal/proximal ureter stones. The certainty of evidence was high or moderate for all outcomes. The main limitation of the review was inconsistency in residual stone assessment methods.ConclusionWhile URS is an effective and safe treatment for stone disease, preoperative alpha‐blocker therapy is well tolerated and can further improve patient outcomes.