BACKGROUND: Autologous plasma rich in platelets (PRP) is a derived blood product whose application in clinical practice is growing. A systematic review was conducted to evaluate its efficacy and safety. STUDY DESIGN AND METHODS:A search was performed in electronic databases. Randomized controlled clinical trials (RCTs) in adult patients were included and assessed for methodologic quality. The main outcomes were "tissue regeneration" and "safety." Relative risks (RRs) and standardized mean differences (SMDs) were calculated to show pooled estimates for these outcomes. When the results heterogeneity was more than 50 percent, a sensitivity analysis was performed. RESULTS: Twenty RCTs were included (11 of oral and maxillofacial surgery, 7 of chronic skin ulcers, and 2 of surgery wounds). Four RCTs evaluated the depth reduction in gingival recession in chronic periodontitis; the SMD was 0.54 (95% confidence interval [CI], 0.16 to 0.92) mm, favorable to PRP. Three RCTs evaluated the clinical attachment level in chronic periodontitis; the SMD was 0.33 (95% CI, -0.71 to 1.37) mm. Six RCTs assessed the complete skin epithelialization in wound ulcers; the RR was 1.40 (95% CI, 0.85 to 2.31). Only 6 RCTs reported adverse effects without differences between groups. CONCLUSIONS: PRP improves the gingival recession but not the clinical attachment level in chronic periodontitis. In the complete healing process of chronic skin ulcers, the results are inconclusive. There are little data about PRP safety. There are several methodologic limitations and, consequently, future research should focus on strong and well-designed RCTs that assess the efficacy and safety of PRP.