The microstructural characteristics of osteoarthritic subchondral bone in the medial tibial condyle are clearly different from normal age-matched bone. Subchondral sclerosis in osteoarthritis indicates not only an increase in bone volume fraction but also alteration in other microstructural characteristics. Eleven medial tibial condyles were collected from ten subjects during arthroplastic surgery for knee oseoarthritis. They were compared to four medial tibial condyles from four age-matched controls with no history of any bone or joint disorder. Six sections from anterior to posterior and three levels from proximal to distal were evaluated in each medial condyle. Five histomorphometric parameters were measured: bone volume fraction (BVf), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.S), and trabecular connectivity (Tb.C). In general, the osteoarthritic subchondral bone had a higher bone volume fraction than control bone but the microstructure was characterized by fewer, widely spaced, thicker than normal trabeculae. There were also highly localized regional differences by depth from the articular surface and from anterior to posterior across the medial condyle. These variations in OA subchondral bone microstructure may significantly affect biomechanical competence of bone in a way not predictable by bone volume fraction measurements alone.