Bone mineral density (BMD) is an important predictor of future fracture risk in women; however, there are few prospective data in men. The aim of this analysis was to determine whether there are differences in the relationship between BMD and incident vertebral fracture in men and women. Men and women were recruited from population-based registers in 21 European centers. Those recruited were interviewed and had spinal radiographs performed. The radiographs were assessed morphometrically and prevalent vertebral deformity was defined using the McCloskey-Kanis method. Repeat spinal radiographs were performed at a mean of 3.8 years after the baseline radiographs. Incident fractures were defined using a combination of the point prevalence and 20% reduction in vertebral height (plus a 4-mm reduction in absolute height) criteria. BMD measurements were made in a subsample of those recruited. Poisson regression was used to explore the influence of gender, age, prevalent deformity, and BMD on the incidence of vertebral fracture. Thirty-four hundred sixty-one men and women had both paired spinal radiographs and bone density measurements performed. BMD at the spine and femoral neck was higher in men than in women. After adjusting for age, the risk of incident vertebral fracture was greater in women than in men (relative risk [RR] = 2.3; 95% CI, 1.5-3.6) and increased by a factor of 1.4 (95% CI, 1.2-1.8), 1.5 (95% CI, 1.2-1.8), and 1.6 (95% CI, 1.3-1.9) per decrease of 0.1 g/cm2 in BMD at the spine, femoral neck, and trochanter, respectively. After adjusting for BMD at the spine or trochanter, the gender difference in the predicted age-specific incidence of vertebral fracture was no longer significant (RR = 1.1 and 95% CI, 0.6-1.9 at the spine; RR = 1.5 and 95% CI, 0.8-2.7 at the trochanter), although it persisted after adjusting for femoral neck BMD (RR = 1.9; 95% CI, 1.1-3.3). The presence of a prevalent vertebral deformity was a strong risk factor for future vertebral fracture, although the strength of the association was reduced after adjustment for age, sex, and spine BMD. However, adjustment for the presence of a baseline vertebral deformity did not alter the main findings. In conclusion, at a given age and spine (although not femoral neck) bone density, the risk of incident vertebral fracture is similar in men and women. Incident vertebral fractures are more common in women than men because at any age their spine BMD is lower.