Purpose: Platelet-rich plasma (PRP) is potentially useful as an adjunct to allograft and xenograft materials in oral and maxillofacial bone and implant reconstructive surgery. This study compares bone healing and formation in 4 cranial defects in rabbits grafted with autogenous bone, xenograft, and xenograft with PRP (with a no-graft group as a control). Materials and Methods: Fifteen New Zealand white rabbits were included in this randomized, blind, prospective pilot study. Four identical 8-mmdiameter defects were created in each rabbit cranium and immediately grafted with the above materials. Five rabbits were evaluated at 1 month, 5 at 2 months, and 5 at 4 months. Radiographs were used to evaluate bone density. Results: Radiographically, sites at which Bio-Oss, autogenous bone, and Bio-Oss + PRP were grafted showed a significant increase in bone density at 1 month (P = .05 for Bio-Oss, P = .02 for autogenous bone, P = .008 for Bio-Oss + PRP) and at 4 months (P = .02 for Bio-Oss, P = .04 for autogenous bone, P = .05 for Bio-Oss + PRP). Autogenous bone sites (P .001) and Bio-Oss + PRP sites (P .001) also showed significant increases at 2 months. Histomorphometrically, autogenous bone sites showed a significantly greater increase than control sites (P = .08 at 1 month, P = .03 at 2 months, P = .01 at 4 months), Bio-Oss sites (P .001 at all 3 evaluation points), or Bio-Oss + PRP sites (P = .009 at 1 month, P = .02 at 2 months, P = .01 at 4 months). Furthermore, Bio-Oss + PRP sites showed a significantly greater increase in bone area at 1, 2, and 4 months than Bio-Oss alone (P = .003 at 1 month, P = .02 at 2 months, P = .006 at 4 months). Discussion: Radiographs showed significantly greater bone density at the Bio-Oss, autogenous bone, and Bio-Oss + PRP sites than at control sites at nearly every point in time evaluated; however, clinical significance is difficult to determine, since all materials appeared dense on the radiograph. Histomorphometry showed that the increase in bone area at autogenous sites was significantly greater than that seen with other grafting materials or at the control sites. Conclusion: This study showed a histomorphometric increase in bone formation with the addition of PRP to Bio-Oss in non-critical-sized defects in the rabbit cranium.