The present study evaluates the effects of leukocyte-platelet-rich fibrin (L-PRF) combined with open flap debridement (OFD) on clinical parameters and growth factors levels (GFL) in chronic periodontitis (CP) patients. This trial was registered at clinicaltrials. gov as NCT02594605. 16 patients (32 sites) with chronic periodontitis who had at least two areas of horizontal bone loss, were treated with OFD alone or L-PRF with OFD (OFDthornL-PRF). GFL in gingival crevicular fluid (GCF) were analyzed at baseline, 1 week, 2 weeks and 4 weeks after operation. Probing depth (PD) and clinical attachment level (CAL) were measured at baseline and 6months postoperatively. PD reduction and CAL gain were significantly higher in the OFDthornL-PRF sites than in OFD sites. OFDthornL-PRF group showed significantly increased bone morphogenetic protein-2 and insulin-like growth factor-1 at 2 weeks compared with baseline. L-PRF combined with OFD significantly increases GFL and thus, it enhances the periodontal healing on CP patients.