This study tests the hypothesis that reduced blood flow to the lower extremities may affect bone remodeling, resulting in a decrease in bone mineral density (BMD). BMD was measured in the axial and appendicular skeleton of 1292 elderly women (mean age, 71 years) enrolled in the Study of Osteoporotic Fractures. The ratio of the posterior tibial and brachial systolic blood pressures, the ankle/arm index, was used as a measure of blood flow to the legs. In the cross-sectional analysis, this index was positively correlated with BMD at the radius, calcaneus, and hip, but not at the spine. A decrease in the index of 2 standard deviations (SD) (as might occur in patients with moderate arterial disease) was associated with a decrease of 3.7% (95% CI, 1.7%, 5.8%) in hip BMD. The effect size at the hip decreased from 3.7 to 1.8% (and was not statistically significant) when adjustment was made for smoking and/or body mass index (BMI). In the prospective analysis, the rate of bone loss at the hip and calcaneus was greater (p < 0.05) among women whose annual decrease in ankle/arm index was more than 1 SD greater than the mean decrease. This increase was independent of estrogen use, smoking, BMI, pattern of fat distribution, history of diabetes, exercise, and ability to walk. The results from this prospective community-based study provide the first evidence that among relatively healthy older women decreased vascular flow in the lower extremities may be associated with an increased rate of bone loss at the hip and calcaneus.