The purpose of the present study was to compare the effects of risedronate (RIS) and alfacalcidol (ALF) on the cortical and cancellous bone mass and mechanical properties in ovariectomized rats in a head-to-head fashion. Forty female Sprague-Dawley rats, 7 mo of age, were randomized into six groups: the sham-operated control (Sham) group, and five ovariectomized groups: treated with vehicle, RIS (0.1, 1.0, or 2.5 mg/kg, p.o., daily), and ALF (0.5 μg/kg, p.o., daily). At the end of the 8-wk experimental period, bone histomorphometric analyses of the cancellous bone of the proximal tibial metaphysis and cortical bone of the tibial disphysis was performed, and the mechanical properties of the bone were evaluated at the femoral distal metaphysis (FDM) and femoral diaphysis (FD). RIS prevented the decrease in the cancellous bone volume/total tissue volume (BV/TV) noted in ovariectomized rats in a dose-dependent manner, by suppressing increases in cancellous bone formation and resorption, without any apparent effect on the Ct Ar or maximum load of the FDM or FD. On the other hand, ALF increased the cancellous BV/TV, Ct Ar, and maximum load of the FDM or FD, by mildly decreasing cancellous bone formation and resorption, increasing periosteal and endocortical bone formation, and preventing an increase in endocortical bone resorption. Thus, the present study clearly showed that RIS and ALF had differential effects on the cortical and cancellous bone mass and mechanical properties in ovariectomized rats.