We evaluate the efficacy and safety of combining antimuscarinics with alpha-blockers to treat storage symptoms in men with benign prostatic hyperplasia. Searches were carried out on PubMed, MEDLINE, EMBASE, and Cochrane databases to identify randomized, placebo-controlled trials published before February 15, 2022, assessing the efficacy or safety of antimuscarinics in men with benign prostatic hyperplasia treated with alpha-blockers. Further meta-analyses were performed using standardized mean difference and risk ratio. A total of 12 randomized trials were included in the systematic review. The meta-analysis showed no impact of antimuscarinics on the number of urgencies per day (SMD -0.23 [95%CI: -0.64; -0.17]; P = .21). However, the use of antimuscarinics was associated with a small reduction of micturition episodes per day (SMD -0.19 [95%CI: -0.37; -0.01]; P = .045). With regard to side effects, post-void residual increased slightly in patients treated with antimuscarinics (SMD 0.26 [95%CI: 0.15; 0.37]; P < .01). In addition, there was a higher risk of acute urinary retention (RR 3.26 [95%CI: 1.35; 7.86]; P = .02), dry mouth (RR 3.43 [95%CI: 1.86; 6.32]; P < .001), and constipation (RR 2.92 [95%CI: 1.48; 5.73]; P < .001) with the use of antimuscarinics. Finally, the risk of treatment interruption due to adverse events was higher for the patients treated with antimuscarinics (RR 1.74 [95%CI: 1.27; 2.38]; P < .01). The addition of antimuscarinics to alpha-blockers was not associated with a substantial reduction in urgencies and micturition episodes in benign prostatic hyperplasia patients with storage symptoms. In addition, the toxicity profile was not in favor of antimuscarinic use in these patients.