The incidence of all non-vertebral fractures, as well as the relation to bone mineral density (BMD), was quantified in 7806 men and women from the Rotterdam Study, a prospective, population-based cohort study of men and women aged 55 years and older. In addition, the sensitivity of using a T-score at or below -2.5 for identifying subjects at risk for fractures was assessed. At baseline, between 1990 and 1993, femoral neck BMD was measured by dual energy X-ray absorptiometry (DXA). Subsequently, gender-specific T-scores were calculated using the NHANES reference population. During a mean follow-up of 6.8 years, information on incident non-vertebral fractures was gathered. In general, hip, wrist and upper humerus fractures are the most frequent fractures in both men and women. Femoral neck BMD appears to be an equally important risk factor in both genders, and is especially related to hip fractures. For all non-vertebral fractures, the age-adjusted hazard ratio (95% confidence interval) per standard deviation decrease in femoral neck BMD was 1.5 (1.4-1.6) for women and 1.4 (1.2-1.6) for men. For hip fractures, the hazard ratios were 2.1 (1.7-2.5) for women and 2.3 (1.6-3.3) for men. Only 44% of all non-vertebral fractures occurred in women with a T-score below -2.5; in men, this percentage was even lower (21%). Thus, there is a clear need for the development of more sensitive risk assessment tools, using not only BMD, but also other clinical predictors of fractures.