BACKGROUND:We performed a systematic review and meta-analysis to determine the prevalence and predictors of urethral stricture development post radiation therapy (RT) for prostate cancer (PCa). METHODS:Published articles in PubMed/Medline, Cochrane, and Embase databases from January 2000 to April 2016 were queried. Inclusion criteria were any study that reported the prevalence of urethral strictures following external beam radiation therapy (EBRT), brachytherapy (BT), or both as a primary treatment for PCa. Forty-six articles met our inclusion criteria. A summary estimate of the proportion of patients who developed a urethral stricture was derived via a random effects meta-analysis. RESULTS:In total, 16,129 PCa patients underwent either EBRT (5681, 35.2%), BT (5849, 36.3%), or both (4599, 28.5%). Overall, 630 strictures were diagnosed at follow-up with a pooled estimate period prevalence of 2.2% (95% confidence interval, CI 1.9-2.6%) in a median follow-up time of 4 years (interquartile range, IQR 2.7-5). Of which, the pooled estimate prevalence was 1.5% (95% CI 0.9-2%) post EBRT, 1.9% (95% CI 1.3-2.4%) post BT, and 4.9% (95% CI 3.8-6%) post both EBRT and BT. Of 20 studies reporting a median time to stricture formation, the overall median time was 2.2 years (IQR 1.8-2.5, range 1.4-9). In a meta-regression analysis, receiving both EBRT and BT increased the estimated difference in proportion of stricture diagnoses by 3% (95% CI 1-6%), p = 0.018 compared to EBRT alone. An increase in median follow-up time was found to significantly increase the risk of developing urethral strictures (p = 0.04). CONCLUSIONS:With a short-term follow-up, urethral strictures occur in 2.2% of men with PCa receiving radiotherapy. Receiving both EBRT and BT increased the risk of stricture formation. Longer follow-up is needed to determine the long-term natural history of stricture formation after RT.