Platelet-rich fibrin versus natural clot healing after mandibular third molar surgery: A systematic review of randomized controlled trials

Objective To evaluate whether platelet-rich fibrin (PRF) improves postoperative and healing outcomes compared with natural clot healing after mandibular third molar surgery. Methods This systematic review focused on randomized controlled trials and was supported by critically appraised systematic reviews to inform contextual interpretation. PubMed/MEDLINE, Scopus, and CENTRAL were searched to March 20, 2026, with additional cross-referencing. Eligible studies compared mandibular third molar surgery with local PRF placement to natural clot healing. The primary outcome was alveolar osteitis. Key secondary outcomes were postoperative pain, analgesic consumption, facial swelling, trismus, and soft-tissue healing. Additional outcomes included periodontal healing distal to the second molar, adverse effects, radiographic or bone healing, and biological or inflammatory markers. Risk of bias was assessed with RoB 2, and certainty of evidence was evaluated using GRADE. A hierarchical narrative synthesis was performed, supplemented by focused exploratory meta-analyses when sufficient extractable, clinically comparable data were available. Results Forty-five randomized controlled trials were included. Focused exploratory meta-analysis showed that PRF reduced alveolar osteitis/dry socket compared with natural-clot control care (RR = 0.35, 95% CI 0.22–0.56; I² = 0%). PRF also showed favorable pooled effects for postoperative pain and swelling at several early time points, although heterogeneity was substantial. L-PRF was meta-analyzed only for pain. A-PRF and i-PRF were retained in the narrative synthesis because quantitative pooling was not feasible. Conclusion PRF probably reduces alveolar osteitis and probably improves soft-tissue healing after mandibular third molar surgery. It may also reduce early postoperative pain and swelling, but certainty remains limited by heterogeneity, variation in natural-clot control protocols, subjective outcome measurement, and risk-of-bias concerns.