Alpha-blockers and antimuscarinics combination therapy has been commonly used for treatment of male lower urinary tract symptoms (LUTS). We conducted a meta-analysis aimed to access the relative efficacy and safety of combination therapy. We systematically searched Medline, Cochrane, and Embase for eligible studies. Fifteen randomized studies with 4556 patients were included. Overall, combination therapy significantly improved the urgency, voiding frequency, International Prostate Symptom Score (IPSS) total scores, and IPSS storage subscores. Addition of antimuscarinics had little effect on urinary function. The incidences of adverse events were acceptably low. Our meta-analysis demonstrated that the combination therapy was a safe, well-tolerated, and effective treatment for male LUTS.