To determine the prevalence of significant left-right differences in hip bone mineral density (BMD), and the impact of this difference on osteoporosis diagnosis, we measured bilateral proximal femora using dual energy X-ray absorptiometry (DXA) in 3481 subjects (608 males, 2873 females). The difference between left and right hip was considered significant if it exceeded the smallest detectable difference (SDD) for any of the three hip subregions. Contralateral femoral BMD was highly correlated at all measuring sites (r = 0.92-0.95). However, significant left-right differences in BMD were common: the difference exceeded the SDD for 54% of patients at total hip, 52.1% at femoral neck, and 57.7% at trochanter. The prevalence of left-right differences was greater in participants >65 years. For 1169 participants with normal spines, 22 (1.9%) had discordant left-right hips in which one hip was osteoporotic; for 1349 patients with osteopenic spines, 94 (7%) had osteoporosis in one hip. Participants with BMI < 20 kg/m(2) were more likely to show major T-score discordance (osteoporosis in one hip and normal BMD in the other). Multiple regression analysis showed that the only significant statically parameter that persists after adjusting for all potential confounding parameters were age over 65 years.