Background: Platelet-rich plasma (PRP) and bioceramics such as hydroxyapatite (HA) and zirconium oxide (ZrO2) are used to reconstruct mandibular defects. We sought to determine the synergistic effects of HA/ZrO2 and PRP and compare their osteogenic activity.Methods: ZrO2 scaffolds were constructed by the slurry method and were then coated with HA and impregnated by PRP/heparan sulfate (HS). Bilateral mandibular defects were created in 26 male rabbits. In 20 rabbits, the left defects were treated with HA/ZrO2/PRP (Group 1) and the corresponding right defects were filled with HA/ZrO2 (Group 2). The 6 remaining models were treated with PRP gels at both sides (Group 3). The osteoconductivity of HA/ZrO2/PRP was compared with that of HA/ZrO2 or PRP by radiological and histological methods after the follow-up period, at weeks 6, 8, and 12. The statistical analyses were performed by ANOVA and LSD using SPSS, version 16.0, for Windows (P<0.05).Results: After 2 weeks, the percentage of the surface occupied by bone was significantly higher in the HA/ZrO2/PRP-treated defects than in the PRP-treated defects (P=0.007). Osteoblast and osteocyte counts were higher significantly in the PRP-treated group (P=0.032); however, the cells had not started matrix formation on a large scale and just small islands of osteoid with trapped osteocytes were observed. In the long term, the regenerative potential of all the scaffolds was the same. Conclusion: HA/ZrO2 showed a superior osteoconductive capacity over PRP in the short term; however, they showed no long-term synergic effects.