Conduct a systematic review and meta-analysis of studies to evaluate the association between the use of PDE5I and biochemical recurrence (BCR) after radical prostatectomy (RP). We searched Embase (from 1996 to Feb 2018), PubMed (from 1996 to Feb 2018), and Cochrane library (from 1999 to Feb 2018), then manually searched the reference lists of key retrieved articles. Original studies that reported the risk of postoperative BCR for PDE5I users, as compared with non-PDE5I users, were included. Data including the characteristic of participants, the risk of BCR after RP and key criteria of study quality were collected. The pooled relative risks (RRs) were calculated with random-effects model. A total of 5 cohort studies and 1 case-control study were conducted for data analysis (a total of 17752 participants). Only 1 cohort study reported adjusted RR greater than 1 (range for all derived RRs, 0.7-1.47). The meta-analysis revealed that the PDE5I users had no higher risk of BCR after RP (RR = 1.04, 95% confidence interval [CI], 0.79-1.36). Sensitivity analysis showed that the remaining pooled RR and 95% CI were not changed significantly by omitting each study. In addition, the 5-year BCR rate had no significant difference between PDE5I users and non-PDE5I users. Our meta-analysis indicated that PDE5I treatment in men following RP did not increase the risk of BCR. The results preliminarily suggested that the use of PDE5I for erectile dysfunction after RP was oncologically safe. Nevertheless, more large sample cohort studies are needed to validate this conclusion.