Background: Recent large high-quality trials have questioned the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones. Objective: To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo. Design, setting, and participants: We conducted a double-blind, placebo-controlled study of 3296 patients with distal ureteral stones, across 30 centers, to evaluate the efficacy and safety of tamsulosin. Intervention: Participants were randomly assigned (1:1) into tamsulosin (0.4 mg) or placebo groups for 4 wk. Outcome measurements and statistical analysis: The primary end point of analysis was the overall stone expulsion rate, defined as stone expulsion, confirmed by negative findings on computed tomography, over a 28-d surveillance period. Secondary end points included time to stone expulsion, use of analgesics, and incidence of adverse events. Results and limitations: Among 3450 patients randomized between September 1, 2011, and August 31, 2013, 3296 (96%) were included in the primary analysis. Tamsulosin benefits from a higher stone expulsion rate than the placebo (86% vs 79%; p < 0.001) for distal ureteral stones. Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones (>5 mm). Considering the secondary end points, tamsulosin-treated patients reported a shorter time to expulsion (p < 0.001), required lower use of analgesics compared with placebo (p < 0.001), and significantly relieved renal colic (p < 0.001). No differences in the incidence of adverse events were identified between the two groups. Conclusions: Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic. Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones >5 mm, but no effect for stones <= 5 mm. (c) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.