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Bone regeneration is a complex process influenced by various physiological factors. Platelet-rich plasma (PRP) contains many growth factors and has shown osteogenic effects. The PRP is usually activated before use. However, the authors showed that nonactivated PRP (nPRP) and activated PRP have comparable osteogenic effects in the previous study. Generally, a scaffold has been needed for the application of PRP in the cranial defect model. In this study, the authors aimed to compare the performance of scaffold free platelet-rich fibrin (PRF) to nPRP as an adjuvant for bone regeneration.Twenty-four New Zealand White rabbits were randomly allocated into 3 groups: control, nPRP, and PRF. A 15 × 15 mm2 defect was created on each rabbit's cranium. Acellular collagen sponges (Gelfoam) were placed on the defects of the control group, Gelfoam with nPRP was used for the nPRP group, and PRF membrane was directly applied for the PRF group. nPRP and PRF were obtained from each subject's peripheral blood. Sixteen weeks later, the volume of regenerated bone was measured using 3-dimensional computed tomography. The surface area was measured via autopsy, and the samples were then obtained for histological analysis.Bone regeneration in the experimental groups was significantly greater than that in the control group. There were no significant differences in the area of regeneration or histological characteristics between the nPRP and PRF groups.In the calvarial defect of the rabbits, the use of PRF and scaffolded PRP showed comparable bone regeneration effects, which suggested that PRF might be a therapeutic alternative for bone grafts.