The aim was to summarize the evidence on the effectiveness and safety of platelet-rich fibrin (PRF) use for patients undergoing third molar surgery. Eligible studies were randomized controlled trials (RCT) that evaluated the use of PRF in third molar surgery. Searches in CENTRAL, MEDLINE, Embase, LILACS, the International Clinical Trials Registry Platform, ClinicalTrials.gov and grey literature were performed. Two reviewers evaluated potentially eligible studies and extracted data. We performed meta-analyses using random-effect models and assessed overall certainty using GRADE. Search strategy yielded 134 studies. We included 28 RCTs, 24 were assessed quantitatively. Overall risk of bias was low for 10,4 % of the outcomes. Recent RCTs generated pooled statistically significant results for the use of PRF in: alveolar osteitis (RR=0.39, IC95 % 0.21 to 0.72); postoperative pain day 1 (SMD=1.19, 95 %CI 1.89 to 0.48) and day 3 (SMD=1.31, 95 %CI 2.07 to 0.55); soft tissue healing day 7 (SMD=0.17, 95 %CI 1.61 to 1.27); oedema day 3 (SMD=1.95, 95 %CI 3.45 to 0.45); and wound infection (RR=0.29, 95 %CI 0.06 to 1.37). Contrasting previous reviews, PRF benefited bone healing at month 2 (SMD=5, 95 %CI 1.02 to 8.98). Certainty of evidence increased from previous reviews to moderate for alveolar osteitis and pain day 3. All other outcomes remained with low and very low confidence in results, thus, the use of PRF may result in little to no difference for these. No adverse events were reported. Recent RCTs have improved the precision and potency of previous reviews’ results, increasing their certainty. PRF likely reduces the risk of alveolar osteitis and pain at day 3 after third molar surgery. Regarding oedema, trismus, infection, soft tissue and bone healing, certainty of evidence remains very uncertain due to small samples and high or unclear risk of bias. Thus, further well-designed RCTs are needed to confirm and expand these results.