This study aimed to test the null hypothesis that platelet-rich fibrin (PRF), as an immediate postextraction graft material, produces bone that is histomorphometrically no different than bone derived from healing without intervention. The authors compared split-mouth human bone biopsy specimens derived from PRF with bone that had healed without intervention. Eight human bone biopsies were successfully harvested from four patients. The mean ± standard deviation (SD) percent of newly formed osteoid was 9.9% ± 5.9% for specimens derived from PRF, and 4% ± 2.1% for specimens derived from the control sites (P = .089; 95% confidence interval [CI] 4.5-18.1 and 1.6-6.6, respectively). Mean ± SD percent of new mineralized bone was 40.8% ± 10.3% for the PRF specimens and 43.9% ± 16.8% for the control specimens (P = .72, 95% CI, 33.4-55.6 and 19.3-55.5, respectively). Newly formed bone to fibrovascular tissue ratios for specimens in the PRF and control groups were 51%:49% and 48%:52%, respectively. Within the limitations of this study, the null hypothesis could not be rejected. Bone derived from PRF histologically did not differ from bone that healed without intervention.