Cancellous bone from patients with osteoarthritis (OA) has a reduced material density and appears to be undermineralized. It is hypothesized that this will result in a reduction in the mechanical stiffness and strength of the bone matrix. In this study, bone was obtained from superior and inferior sites, subjected to relatively high and low loads, respectively, from human femoral heads retrieved after surgery for osteoporotic hip fracture (OP), or for hip arthroplasty due to OA. Microindentation testing was used to measure the hardness of cancellous bone at various depths from the subchondral bone plate. The elemental composition from immediately adjacent microscopic sites was determined using electron probe microanalysis (EPMA). Overall, OA bone was found to have hardness values that were 7% lower than those from OP bone. Bone from the inferior site was harder than that from the superior in both diseases except in female OP patients. There was no variation with depth below the subchondral plate and no difference between sexes. No difference was found in the composition of the bone from the different disease groups and no correlation was found between hardness and any of the composition measurements. Though only an indirect measurement of stiffness, the reduction in hardness values supports the hypothesis that OA bone has a reduced elastic modulus.