The purpose of this study was to evaluate the diagnostic sensitivity of phalangeal bone ultrasound velocity of the hand in the diagnosis of osteoporosis and to compare this technique to bone mineral density (BMD) measurement at the lumbar spine assessed by dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). We investigated US velocity at the distal metaphysis of the proximal phalanx and spinal BMD in 101 women. Fifty-nine were healthy (mean age 50 ± 11.6 years) and 42 were osteoporotic (mean age 65 ± 6.6 years) with documented vertebral fractures. In the healthy population the relation with age was, respectively, r = –0.73 (p < 0.0001) for quantitative US (QUS), r = –0.74 (p < 0.0001) for QCT and r = –0.48 (p < 0.01) for DXA. Both US and DXA were correlated with QCT: r = 0.74 and r = 0.77 (p < 0.0001), respectively. Correlation of QUS and DXA was r = 0.56 (p < 0.0001). Phalangeal US velocity and spinal BMD (QCT and DXA) values discriminate healthy from osteoporotic women. Age-adjusted logistic regression analysis of the data showed standardized odds ratios (OR) for vertebral fracture to be similar for US and DXA (OR = 1.8 and 1.5, respectively) and stronger for QCT (OR = 2.9). Phalangeal US velocity reflects age-related bone loss and differentiates between healthy and osteoporotic subjects.