Aim: The aim of this double-blinded, randomized, controlled clinical study was to investigate the effect of titanium-prepared platelet-rich fibrin (T-PRF) treatment on the angiogenic biomarkers in gingival crevicular fluid (GCF) in infrabony defects of patients with chronic periodontitis. Materials and Methods: Twenty five systemically healthy participants who complied with inclusion criteria with periodontal infrabony defects were recruited. In each patient, the infrabony defect of one side of arch was designated as control group (allograft), whereas the infrabony defect on the contralateral side of same arch was designated as test group (allograft + T-PRF). The therapy methods (test or control) were randomly decided. GCF samples were collected at baseline (presurgery) and then the 3rd, 7th, 14th, and 30th days after surgery. Platelet-derived growth factor (PDGF)-BB, vascular endothelial growth factor (VEGF)-A, fibroblast growth factor (FGF)-2, anjiogenin (ANG), angiostatin (ANT) in the GCF samples were measured using human enzyme-linked immunosorbent assay kits. Results: In both groups, total amounts of PDGF-BB, VEGF-A, FGF-2, ANG, and ANT peaked in the GCF samples obtained at the early postoperative day (day 3) and decreased over time in the samples obtained at the 7th, 14th, and 30th days postsurgery. There were no significant differences between groups for the total amounts of PDGF-BB, VEGF-A, FGF-2, ANG, and ANT at all evaluation periods. Conclusion: Application of T-PRF combined with allograft in infrabony defects of patients with chronic periodontitis had no significant effects on angiogenic biomarkers in GCF.