Background and Objectives: The aim of the present systematic review and meta-analysis was to investigate the efficacy of leukocyte-platelet-rich fibrin (L-PRF) in addition to coronally advanced flap (CAF) for the treatment of both single and multiple gingival recessions (GRs) compared to the CAF alone and to the adjunct of connective tissue graft (CTG). Root coverage outcomes using platelet concentrates have
gained increased interest. In particular, it has been suggested that adding L-PRF to CAF may provide further benefits in the treatment of GRs. Materials and Methods: An electronic and manual literature search was conducted to identify randomized controlled trials (RTCs) investigating root coverage outcomes with CAF + L-PRF. The outcomes of interest included mean root coverage (mRC), recession reduction, keratinized tissue width (KTW) gain, gingival thickness (GT) gain, and patient-reported outcome measures (PROms) such as pain perception and discomfort. Results: A total of 275 patients and 611 surgical sites were analyzed. L-PRF in adjunct to single CAF seems to show statistically significant results regarding clinical attachment level (CAL) with a weighted means (WM) 0.43 95% CI (-0.04,0.91), p < 0.0001, GT (WM 0.17 95% CI (-0.02,0.36), p < 0.0001, and mRC (WM 13.95 95% CI (-1.99,29.88) p < 0.0001, compared to single CAF alone. Interesting results were obtained from the adjunct of PRF to multiple CAF with respect to multiple CAF alone with an increase in the mRC WM 0.07 95% CI (-30.22,30.35), p = 0.0001, and PPD change WM 0.26 95% CI (-0.06,0.58), p < 00001. On the other hand, no statistically significant data were obtained when L-PRF was added to single or multiple CAF combined with CTG according to the included outcomes such as mRC (p = 0.03 overall). Conclusions: L-PRF is a valid alternative to CAF alone. L-PRF compared to CTG in single and multiple CAF showed statistically significant results regarding pain perception and discomfort PROms (p < 0.0001). However, CTG remains the gold standard for treating gingival recession.