Previous studies have reported the clinical efficacy of avanafil for erectile dysfunction (ED), but these findings are controversial. This study aims to investigate the safety and efficacy of avanafil for ED. EMBASE, PubMed, and Cochrane Library were searched extensively to obtain eligible studies. Clinical outcomes including successful vaginal penetration (SVP), successful intercourse (SI), International Index of Erectile Function-Erectile Function domain (IIEF-EF) score and treatment adverse events (TAEs) were compared using RevMan v.5.3. Eight RCTs involving 3,709 patients were included. The analysis demonstrated that compared with placebo, the SVP (RR = 3.20, 95% CI [2.60, 3.95], p < .001), SI (RR = 2.53, 95% CI [2.19, 2.92], p < .001), change in IIEF-EF score (MD = 4.57, 95% CI [3.68, 5.46], p < .001) and TAEs (RR = 1.78, 95% CI [1.38, 2.31], p < .0001) were significantly higher in the avanafil. In addition, avanafil 200 mg were higher than avanafil 100 mg in SI (RR = 0.86, 95% CI [0.75, 0.99], p = .03) and change in IIEF-EF score (MD = -1.34, 95% CI [-1.67, -1.01], p < .001), but there were no obvious differences in SVP (RR = 0.89; 95% CI [0.74, 1.08], p = .23) and TAEs (RR = 0.97, 95% CI [0.83, 1.14], p = .74) between the two doses. The present evidence suggests that avanafil (especially 200 mg) has the potential to be the drug of choice for ED, but more strict and larger sample size RCTs are need to validate the findings.