Objective: Platelet-rich fibrin (PRF) is a fibrin matrix in which platelet cytokines, growth factors and cells are embedded; therefore, it has the potential to be used as regenerative therapy. The aim of this randomized clinical study was to evaluate the regenerative capacity of PRF when compared to collagen membrane (CM) for the treatment of intrabony periodontal defects in patients with generalized aggressive periodontitis (GAgP). Methods: Using a split-mouth design, sixteen GAgP patients with paired contralateral intrabony defects were randomly assigned to the test group (composite bone graft {autogenous bone mixed with xenograft} + PRF, n = 16 sites) and control group (composite bone graft + CM, n = 16 sites). Plaque index, papillary bleeding index, probing pocket depth (PPD), clinical attachment level (CAL) and position of gingival margin (GML) were recorded prior to surgery and 6 months after surgery. The percentage of defect resolution (DR) was calculated radiographically at 6 months after surgery by intraoral periapical radiographs. Primary study outcome was change in CAL. Results: Six-month results indicated that both treatment modalities resulted in a significant reduction in PPD, gain in CAL, and DR (p < 0.05). A statistically significant improvement in GML was recorded for the test group (p < 0.05) but not for the control. Intergroup comparison was insignificant for all parameters (p > 0.05) except for GML (p < 0.05). Conclusions: Platelet-rich fibrin has shown favorable results that are comparable to CM for treatment of intrabony periodontal defects in patients with GAgP. However, better results concerning GML have been reported when PRF was used.