AimThe current randomized controlled clinical trial assessed the effect of injectable platelet-rich fibrin (I-PRF) combined with demineralized freeze-dried bone allograft (DFDBA) compared to DFDBA alone in the management of intrabony defects of stage-III periodontitis patients.MethodologyFollowing sample size calculation, twenty stage-III periodontitis patients with ≥ 5 mm clinical attachment level (CAL)-loss and ≥ 3 mm intrabony defects were randomized into test (I-PRF + DFDBA;n= 10) and control (DFDBA;n= 10) groups. CAL (primary outcome), periodontal probing depth (PPD), gingival recession depth (GRD), full-mouth plaque scores (FMPS), full-mouth bleeding scores (FMBS), radiographic linear defect depth (RLDD), and bone fill (secondary outcomes) were examined at baseline, 3, 6, and 9 months post-surgically.ResultsI-PRF + DFDBA and DFDBA independently demonstrated significant intragroup CAL-gain, PPD-, and RLDD-reduction at 3, 6, and 9 months (p< 0.05), with no significant intergroup differences observed (p> 0.05). CAL-gain (mean ± SD) of 2.40 ± 0.70 mm and 2.50 ± 0.85 mm and PPD-reduction of 3.50 ± 1.18 mm and 2.80 ± 0.42 mm were demonstrated for I-PRF + DFDBA and DFDBA at 9 months respectively. Both groups showed significant intragroup RLDD improvement, with a RLDD of 3.58 ± 0.66 mm and 3.89 ± 1.57 mm for I-PRF + DFDBA and DFDBA at 9 months respectively. Stepwise linear regression analysis revealed that baseline RLDD and bone fill at 9 months were significant predictors of CAL (p< 0.05).ConclusionWithin the present study’s limitations, DFDBA with or without I-PRF resulted in significant improvement in clinical and radiographic periodontal parameters in the surgical treatment of periodontal intrabony defects of stage-III periodontitis patients. Addition of I-PRF to DFDBA does not appear to significantly enhance the DFDBA’s reparative/regenerative outcomes.Clinical relevanceWithin the current study’s limitations, routinely adding I-PRF to DFDBA cannot be recommended to significantly improve DFDBA’s treatment outcomes in intrabony defects.