This study compared the clinical effectiveness of a combination therapy consisting of bovine porous bone mineral (BPBM), guided tissue regeneration (GTR), and platelet-rich plasma (PRP) in the regeneration of periodontal intrabony defects in humans. Twentyeight paired intrabony defects were surgically treated using a split-mouth design. Defects were treated with BPBM, GTR, and PRP (experimental), or with open-flap debridement (control). Clinical parameters evaluated included changes in attachment level, pocket depth, and defect fill as revealed by reentry at 6 months. Preoperative pocket depths, attachment levels, and transoperative bone measurements were similar for the two groups. Postsurgical measurements taken at 6 months revealed that both treatment modalities significantly decreased pocket depth and increased clinical attachment and defect fill compared to baseline. The differences between the experimental and control groups were 2.22 ± 0.39 mm on buccal and 2.12 ± 0.34 mm on lingual sites for pocket depth, 3.05 ± 0.51 mm on buccal and 2.88 ± 0.46 mm on lingual sites for gain in clinical attachment, and 3.46 ± 0.96 mm on buccal and 3.42 ± 0.02 mm on lingual sites for defect fill. These differences between groups were statistically significant in favor of the experimental defects. The combined therapy was also clinically more effective than open-flap debridement. The superiority of the experimental group could not be attributed solely to the surgical intervention and was likely a result of the BPBM/GTR/ PRP application. Combining BPBM, GTR, and PRP was an effective modality of regenerative treatment for intrabony defects in patients with advanced periodontitis.