Synthetic bone grafts provide an alternative to autografts and allografts. Bonelike® is a patented synthetic bone graft that mimics the mineral composition of bone. The aim of the present work was to assess the biological behavior of Bonelike® graft in humans, before using the material in orthopedic applications of bone regeneration, for example, in opening wedge high tibial osteotomies for medial knee osteoarthritis. Bonelike® granules were implanted in cortical bone of 11 patients undergoing osteotomies, and new bone formation, osteoconductive properties, and resorption characteristics of the granules were analyzed. The granules ranged from 500 to 1000 μm and were implanted in the lateral aspect of the tibia. The patients' mean age was 59 years (range 48 to 70 years); there were eight women and three men, all suffering from medial compartment osteoarthritis of the knee. At surgery, a 1×1×1-cm cortical defect was created 3 cm distal to the entry point of the screws, in line with the long axis of tibia. The implanted Bonelike® graft sample was extracted for analysis during removal of the metallic prosthesis after implantation times of 6, 9, and 12 months. Radiological follow-up, scanning electron microscopy, histological analysis, and histomorphometric measurements were conducted on the retrieved samples to assess bone regeneration in the defect area. Osteoconductive capacity was demonstrated by extensive mature bone formation around the implanted granules and high levels of percentage bone-to-graft contact (from 67-84%). Bonelike® acted as an excellent bioactive scaffold, allowing the migration, proliferation, and differentiation of bone cells on its surface, and therefore regeneration of the defects was achieved in a rapid, controlled manner. Our results suggest that Bonelike® graft is an excellent candidate for orthopedic applications where rapid new bone formation is a fundamental requirement.