Introduction: In a previous study, we successfully prepared fluorinated porcine hydroxyapatite (FPHA) by immersing porcine hydroxyapatite (PHA) in an aqueous solution of 0.25 M sodium fluoride (NaF) under thermal treatment, and the resulting FPHA showed better physicochemical and biological properties than PHA. The purpose of this study was to further investigate how fluorine incorporation influenced the biocompatibility and osteogenic capacity of PHA. Materials and methods: The concentrations of Ca, P, F, and Mg ions in PHA and FPHA extracts were detected by ICP-OES. Rat bone marrow stromal cells (rBMSCs) were treated with PHA and FPHA extracts, and the effects of these extracts on cell proliferation and osteoblastic differentiation were evaluated via CCK-8 assay, alkaline phosphatase assay, and RT-qPCR. For the in vivo assessment, PHA and FPHA were implanted into subcutaneous pockets (n = 6) and rat calvarial defects (diameter = 5 mm, n = 14) for 12 weeks to determine their biocompatibility and osteogenic capacity using micro-CT and histological analysis. Results: FPHA extracts, which release higher concentrations of F and Mg ions, better promoted the osteoblastic differentiation of rBMSCs in vitro. The result of biocompatibility evaluation confirmed the host response and chronic inflammation cells infiltration degree around PHA and FPHA granules were similar. Micro-CT and histological analysis showed more new mineralized bone formation in rats with FPHA-treated defects than in rats with PHA-treated defects. Conclusion: The results of in vitro and in vivo tests consistently indicate that fluorine incorporation effectively enhanced the osteogenic capacity of PHA.