Background: Titanium-prepared platelet rich fibrin (T-PRF) is an autologous hemo-component with a high concentration of platelets that also incorporates leukocytes, and growth factors into the dense fibrin matrix and can be used as a healing biomaterial. This study assesses the adjunctive use of T-PRF in intrabony defects (IBDs) with open flap debridement (OFD) in comparison with guided tissue regeneration (GTR) as a gold standard and OFD alone as a control. Material and Methods: A total of 45 patients (15 per group) were randomized as either T-PRF (test group), GTR (test group), or OFD alone (control group) sites. Probing depth (PD), clinical attachment level (CAL), and IBD were recorded. The radiographic depth of IBD was also measured. Primary outcomes assessed were changes in PD, CAL, and radiographic IBD that were assessed at the beginning and nine months later. Results: The PRF and GTR group showed significant improvement in clinical parameters compared with the OFD alone (control group) at nine months. While there were no significant differences in PD and CAL between test groups (T-PRF and GTR groups), the significant difference was found in radiographic IBD depth. Conclusion: T-PRF may give similar successful results as GTR in the treatment of IBDs with endo-perio lesions.