We have previously demonstrated that octacalcium phosphate (OCP) collagen composite (OCP/collagen) promotes bone regeneration in a critical-sized bone defect of a rodent or canine model. This study was designed to investigate the bone regeneration of OCP/collagen in human bone defect as a first clinical trial. Two patients who had a radicular cyst or apical periodontitis consented to participate in our clinical study, and OCP/collagen was implanted into the defects after operation. Radiographic examination showed effective bone healing in each bone defect at 3 or 6 months. Likewise, computed tomography value significantly increased after implantation. Postoperative wound healing was uneventful, and neither infection nor allergic reaction against OCP/collagen was observed for the entire period. This study demonstrated that OCP/collagen would be safely used and enhanced bone regeneration in human bone defects. To reinforce the efficacy of OCP/collagen as a bone substitute material, it should be compared with other suitable comparators in the future.