Background: Recombinant human platelet-derived growth factor (PDGF) is safe and effective for the treatment of periodontal defects in short-term studies up to 6 months in duration. We now provide results from a 36-month extension study of a multi-center, randomized, controlled clinical trial evaluating the effect and long term stability of PDGF-BB treatment in patients with localized severe periodontal osseous defects. Methods: A total of 135 participants were enrolled from 6 clinical centers for an extension trial. 83 individuals completed the study at 36 months and were included in the analysis. The study investigated the local application of β-tricalcium phosphate scaffold matrix with or without two different dose levels of PDGF (0.3 mg/mL PDGF-BB or 1.0 mg/mL PDGF-BB) in patients possessing one localized periodontal osseous defect. Composite analysis for clinical and radiographic evidence of treatment success was defined as percentage of cases with CAL ≥ 2.7 mm and linear bone growth (LBG) ≥ 1.1 mm. Results: The participants exceeding this composite outcome benchmark in the 0.3 mg/mL rhPDGF-BB group went from 62.2% at 12 m, 75.9% at 24m to 87.0% at 36 m compared to 39.5%, 48.3%, and 53.8% respectively in the scaffold control group at these same time points (p<0.05). Although there were no significant increases in CAL and LBG at 36 months among all groups, there were continued increases in CAL gain, LBG and % bone fill over time suggesting overall stability of the regenerative response. Conclusions: PDGF-BB in a synthetic scaffold matrix promotes long-term stable clinical and radiographic improvements as measured by composite outcomes for CAL gain and LBG for patients possessing localized periodontal defects ( ClinicalTrials.gov number CT01530126).