The purpose of this study was to assess the effects of lasofoxifene on the reproductive system in ovariectomized nonhuman primates. This was a 2-year, randomized study. Adult female macaques (Macaca fascicularis) were assigned randomly into 5 groups: ovariectomized, placebo-treated controls (n = 22); sham-ovariectomized, placebo-treated controls (n = 24); ovariectomized animals given 0.021 mg Premarin kg/d (conjugated equine estrogen; n = 25); lasofoxifene at 1.0 mg/kg/d (n = 23); or lasofoxifene at 5.0 mg/kg/d (n = 25). Outcomes included organ weights and histopathologic findings. Lasofoxifene did not increase uterine weight or endometrial thickness and did not change mammary, vaginal, or cervical histologic condition. Mild endometrial fibrosis and cystic change were seen in lasofoxifene-treated animals, in contrast to significant uterine weight increases and endometrial hyperplasia induced by conjugated equine estrogen. Lasofoxifene did not increase uterine weight and produced minor histologic uterine changes at the doses that were given and had no effect on the breast, vagina, or cervix.