BACKGROUND: Tadalafil is being investigated for the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH-LUTS). OBJECTIVE: To assess efficacy, including onset, and safety of tadalafil on BPH-LUTS and the subject's and clinician's perception of changes in urinary symptoms. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, placebo-controlled, 12-week trial enrolled men ≥45 yr of age with BPH-LUTS for >6 mo, International Prostate Symptom Score (IPSS) ≥13, and maximum urine flow rate (Q(max)) ≥4 to ≤15 ml/s. INTERVENTION: Tadalafil 5mg (n=161) or placebo (n=164), once daily. MEASUREMENTS: Analysis of covariance (ANCOVA) modeling evaluated change from baseline in continuous efficacy variables. Categoric efficacy variables were analyzed with the Cochran-Mantel-Haenszel test, and between-group differences in treatment-emergent adverse events (TEAEs) were assessed using the Fisher exact test. RESULTS AND LIMITATION: Tadalafil significantly improved IPSS results, from baseline to endpoint, compared to placebo (-5.6 vs -3.6; p=0.004). Reduction in IPSS results was apparent after 1 wk and significant after 4 wk (tadalafil -5.3 vs placebo -3.5; p=0.003). The BPH Impact Index (BII) was not assessed at week 1; however, BII improvement was apparent at 4 wk (tadalafil -1.8 vs placebo -1.2; p=0.029) and continued at 12 wk (tadalafil -1.8 vs placebo -1.3; p=0.057). Tadalafil significantly improved the International Index of Erectile Function-Erectile Function score in sexually active men with erectile dysfunction (ED; 6.7 vs 2.0; p<0.001) at 12 wk (not assessed at week 1). Few subjects reported one TEAE or more (p=0.44). For tadalafil, the most common TEAEs were headache (3.7%) and back pain (3.1%). Tadalafil did not significantly improve Q(max) or reduce postvoid residual volume. CONCLUSIONS: Tadalafil 5mg once daily for 12 wk resulted in a clinically meaningful reduction in total IPSS results as early as 1 wk and achieved statistical significance at 4 wk in men with BPH-LUTS. The adverse event profile was consistent with that previously reported in men with ED. TRIAL REGISTRATION: This clinical trial is registered on the clinicaltrials.gov website (http://www.clinicaltrials.gov). The registration number is NCT00827242.