The aim of this study was to test whether recombinant human platelet-derived growth factor BB (rhPDGF-BB) enhances bone regeneration in combination with Β-tricalcium phosphate (Β-TCP) granules or deproteinized bovine bone mineral (DBBM) compared to empty defects and Β-TCP granules alone. Four titanium cylinders were placed on the external cortical plates of seven rabbits' calvaria and randomly allocated to one of four groups: (1) empty, (2) Β-TCP, (3) Β-TCP + rhPDGF-BB, and (4) DBBM + rhPDGF-BB. The mean area of bone regeneration was 13.9% ± 8.4% (empty), 24.0% ± 14.8% (Β-TCP), 37.1% ± 8.9% (Β-TCP + rhPDGF-BB), and 64.4% ± 5.4% (DBBM + rhPDGF-BB), with the greatest bone regeneration noted for DBBM + rhPDGF-BB (P < .01). The fraction of bone substitute material varied between 48.3% ± 9.3% (DBBM + rhPDGF-BB), 53.1% ± 10.6% (Β-TCP + rhPDGF-BB), and 58.0% ± 14.8% (Β-TCP). rhPDGF-BB combined with DBBM showed the greatest potential to enhance bone regeneration.