We studied articular calcified cartilage (ACC) and the immediately subchondral bone (SCB) in normal and osteoarthritic human femoral heads. Thick slices of human normal reference post mortem (PM) and osteoarthritic (OA) femoral heads (age 55–89 years) were embedded in PMMA, micromilled, carbon coated and studied using quantitative backscattered electron (qBSE) imaging to determine variations in degree of mineralization. With exact microanatomical location, nanoindentation was performed on the same block faces in representative superior (more highly loaded) and medial regions of the joint surface. Using a partial unloading method, elastic modulus as a function of indenter penetration depth was determined using a spherical tipped diamond indenter. A pointed indenter was used to determine the tissue hardness in selected locations. The relationship between mineralization and indentation modulus was more distinct in ACC than in SCB, the latter having a higher matrix concentration with variable collagen orientation. In OA, the bulk of the measurements were coincident with those in the PM samples, although there was a greater range in the levels of mineralization and modulus in ACC. In OA, extremely hypermineralized ACC was found in ACC proper, especially in superior regions, and translocated into SCB and hyaline cartilage. The very highly mineralized cartilage fragments may function as a hard grinding abrasive, accelerating wear rates whether attached to or fragmented from the eburnated surfaces of OA ACC. Highly mineralized regions would also alter loading patterns and thereby contribute to further destruction of the joint tissues.