Purpose: Bioactive glass bonds to bone through a calcium phosphate layer that mimics the structure of the mineral phase of bone. Formation of this layer is inhibited in the presence of serum protein. The authors hypothesize that creation of a calcium phosphate layer on the surface of bioactive glass before implantation will enhance bone regeneration and graft material resorption in bone defects. Materials and Methods: Bioactive glass particles covered with a layer of amorphous calcium phosphate (BG-ACP), bioactive glass particles covered with a layer of hydroxycarbonate apatite (BG-HCA), and unmodified bioactive glass particles (as a control) were prepared and implanted in cortical bone defects in dogs or in human maxillary cavities. Ungrafted sites were also used as a control. Results: Histomorphometric analyses showed significantly more bone tissue regeneration and graft material resorption in the defects filled with BG-HCA than in those filled with BG-ACP or unmodified bioactive glass (P .0001). Moreover, measurements of radiographic density of the grafted areas suggested a higher rate of bone regeneration in defects filled with the modified bioactive glass than in those filled with unmodified bioactive glass or in the ungrafted control. Bone formation was significantly greater in defects filled with unmodified bioactive glass particles than in ungrafted defects. Discussion: The enhancement of bone regeneration could be explained by the ability of the apatite layer to facilitate bone adsorption and enhance calcium release, which stimulates osteoblast differentiation and bone formation. Conclusion: Results of both the clinical and animal studies suggest that the use of surfacemodified bioactive glass covered with a hydroxycarbonate apatite layer has the potential to accelerate bone formation and graft material resorption better than unmodified bioactive glass.