Clinical Outcomes of Platelet-Rich Fibrin in Endodontic Microsurgery: A Systematic Review and Meta-Analysis

Background/Objectives: Platelet-rich fibrin (PRF) and its derivatives have been proposed as biological adjuncts to enhance tissue healing following endodontic microsurgery (EMS). However, current evidence regarding their effects on postoperative recovery and long-term bone regeneration remains inconsistent. This study aimed to evaluate the efficacy of PRF and its derivatives as adjuncts in endodontic microsurgery by separately assessing patient-centered postoperative outcomes and radiographic and volumetric bone-healing outcomes through a systematic review and meta-analysis. Methods: This systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261400163). Randomized controlled trials and comparative clinical studies evaluating PRF or its derivatives as adjuncts to EMS were eligible. MEDLINE/PubMed, Embase, Scopus, Web of Science, Cochrane CENTRAL, and reference lists were searched from inception to April 2026. Outcomes included postoperative pain, edema, quality of life, clinical–radiographic healing, CBCT volumetric bone regeneration, bone density, and outcomes in complex defects. Risk of bias was assessed using RoB 2 and ROBINS-I. Random-effects meta-analyses were performed where appropriate, and certainty of evidence was evaluated using the GRADE approach. Results: Seventeen clinical reports corresponding to sixteen independent datasets were included. PRF and its derivatives improved early postoperative recovery, particularly postoperative pain during the first postoperative week. Meta-analysis demonstrated a significant reduction in early postoperative pain favoring PRF-based interventions (SMD/Hedges g = −0.62; 95% CI, −1.03 to −0.21; p = 0.003). Evidence regarding long-term bone regeneration and clinical–radiographic healing remained heterogeneous and inconclusive. CBCT-based studies suggested accelerated early bone healing, although no consistent superiority was demonstrated at 6–12 months. The certainty of evidence ranged from moderate for postoperative pain to very low for volumetric bone regeneration. Interpretation of the findings is limited by clinical and methodological heterogeneity and the small number of studies available for several outcomes. Conclusions: The available evidence suggests that PRF may improve early postoperative recovery and soft-tissue healing after endodontic microsurgery. However, current evidence does not support PRF as a predictable substitute for bone grafts or regenerative biomaterials in large or non-contained defects. Well-designed CBCT-based randomized clinical trials with standardized outcome measures are needed.