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Platelet-rich fibrin (PRF) is a second-generation platelet concentrate which allows one to obtain fibrin membranes enriched with platelets and growth factors, after an anticoagulant-free blood harvest. However, limited information is currently available concerning the biologic effects of PRF on periodontally related cells. To provide clear evidence for the clinical use of PRF, we investigated the biologic effects of PRF on human gingival fibroblasts (GFs), periodontal ligament (PDL) cells, oral epithelial cells, and osteoblasts. Materials and methods: Blood collection was carried out on 10 healthy volunteers. PRF was obtained by centrifugation at 3000 rpm for 12 minutes with a PC-02 table centrifuge. Primary cultured human GFs and PDL cells, the GNM oral epithelial cell line, and the U2OS osteoblast cell line were used to evaluate cell viability and proliferation resulting from PRF according to trypan blue and tetrazolium bromide reduction assays. Results: PRF did not interfere with cell viability of periodontally related cells (P > 0.05). PRF stimulated cell proliferation of osteoblasts (135% of the control), PDL cells (130% of the control), and GFs (120% of the control) during a 3-day culture period (all P < 0.05). However, PRF suppressed oral epithelial cell growth to as low as 80% of the control (P < 0.05). In addition, GFs, PDL cells, and osteoblasts were observed to attach at the margins of PRF by phase-contrast microscopy. Conclusion: Our results suggest that PRF modulates cell proliferation in a cell type- specific manner. These cell type-specific actions may be beneficial for periodontal regeneration.