Raloxifene (RAL) and alendronate (ALN) improve the biomechanical properties of bone by different mechanisms. The goal here was to investigate the effects of combination treatment of RAL and ALN on the biomechanical properties of vertebral bone. Six-month-old Sprague-Dawley rats (n = 80) were randomized into five experimental groups (sham, OVX, OVX + RAL, OVX + ALN, and OVX + RAL + ALN; n = 16/group). Following euthanization, structural and derived material biomechanical properties of vertebral bodies were assessed. Density and dynamic histomorphometric measurements were made on cancellous bone. The results demonstrate that the structural biomechanical properties of vertebral bone are improved with the combination treatment. Stiffness and ultimate load of the OVX + RAL and OVX + ALN groups were significantly lower than those of sham animals, but the combination treatment with RAL + ALN was not significantly different from sham. Furthermore, the OVX + RAL + ALN group was the only agent-treated group in which the ultimate load was significantly higher than that in OVX animals (p < .05). Cancellous bone fractional volume (BV/TV~canc~) and bone mineral density (aBMD) also were improved with the combination treatment. BV/TV~canc~ of the OVX + RAL + ALN group was 6.7% and 8.7% greater than that of the OVX + RAL (p < .05) and OVX + ALN (p < .05) groups, respectively. Areal BMD of the OVX + RAL or OVX + ALN groups was not significantly different from that in OVX animals, but the value in animals undergoing combination treatment was significantly higher than that in OVX or OVX + RAL animals alone and not significantly different from that in sham-operated animals. Turnover rates of both the RAL + ALN and ALN alone groups were lower than in the RAL-treated alone group (p < .05). We conclude that the combination treatment of raloxifene and alendronate has beneficial effects on bone volume, resulting in improvement in the structural properties of vertebral bone. Β© 2011 American Society for Bone and Mineral Research.