Heat-treated bovine cortical bone has been proposed as an alternative to bone grafts and synthetic bone substitutes because it may combine the advantages of allografts (high stiffness and strength) and synthetic materials (abundant supply, reduced risk of rejection and disease transfer). Its mechanical properties and ultrastructure, however, are not well characterized. To address this, we compared the compressive (n = 20, bovine bone) and tensile (n = 26, bovine bone) mechanical properties and the ultrastructure (n = 12, human bone) of intact versus 350ยฐC heat-treated cortical bone. The 350ยฐC heat-treated bone had a mean ยฑ SD elastic modulus similar to the intact bone for both compression (16.3 ยฑ 2.2 GPa, pooled; p = 0.68) and tension (16.3 ยฑ 3.7 GPa, pooled; p = 0.95). It also maintained 63% of the intact strength in compression but only 9% in tension (p < 0.001). Infrared scans and X-ray diffraction patterns showed no differences between the 350ยฐC heat-treated and intact bone but large differences between ashed (700ยฐC) and intact bone. Similarly, heat-treated bone previously has been shown to be biocompatible and osteoconductive. We conclude, therefore, that 350ยฐC heat-treated cortical bone may be an excellent load-bearing bone substitute provided that it is loaded in compression only in vivo and is shown by future work to have acceptable fatigue properties.