Objective: Recombinant human growth/differentiation factor-5 (rhGDF-5) is being evaluated as a candidate therapy in support of periodontal regeneration. The objective of this study was to evaluate periodontal wound healing/regeneration following the application of rhGDF-5 on a particulate β-tricalcium phosphate (β-TCP) carrier using an established defect model. Materials and Methods: Bilateral 4 × 5 mm (width × depth), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular second and fourth pre-molar teeth in 15 Beagle dogs. Unilateral defects in five animals received rhGDF-5/β-TCP (Scil Technology GmbH); five animals received β-TCP solo; and five animals served as sham-surgery controls. Contralateral sites received treatments reported elsewhere. The animals were sacrificed following an 8-week healing interval for histological examination. Results: Clinical healing was generally uneventful. Sites implanted with rhGDF-5/β-TCP exhibited greater enhanced cementum and bone formation compared with β-TCP and sham-surgery controls; cementum regeneration averaged (± SD) 3.83 ± 0.73 versus 1.65 ± 0.82 and 2.48 ± 1.28 mm for the controls (p<0.05). Corresponding values for bone regeneration height averaged 3.26 ± 0.30 versus 1.70 ± 0.66 and 1.68 ± 0.49 mm (p<0.05), and bone area 10.45 ± 2.26 versus 6.31 ± 2.41 and 3.00 ± 1.97 mm2 (p<0.05). Cementum regeneration included cellular/acellular cementum with or without a functionally oriented periodontal ligament. A non-specific connective tissue attachment was evident in the sham-surgery control. Controls exhibited mostly woven bone with primary osteons, whereas rhGDF-5/β-TCP sites showed a noticeable extent of lamellar bone. Sites receiving rhGDF-5/β-TCP or β-TCP showed some residual β-TCP granules apparently undergoing biodegradation without obvious differences between the sites. Sites receiving β-TCP alone commonly showed residual β-TCP granules sequestered in the connective tissue or fibrovascular marrow. Conclusion: rhGDF-5/β-TCP has a greater potential to support the regeneration of the periodontal attachment. Long-term studies are necessary to confirm the uneventful maturation of the regenerated tissues.