To determine if measuring skeletal status at the calcaneus is a potentially valuable technique for diagnosing osteoporosis, we examined five calcaneal assessment techniques in 53 young normal women and 108 postmenopausal women with osteoporosis and compared these measurements to dual-energy X-ray absorptiometry (DEXA) at the calcaneus, hip, and spine. The five instruments, including single-energy X-ray absorptiometry (SEXA) and four quantitative ultrasound (QUS) instruments, were evaluated for precision, ability to discriminate osteoporotic from young normal subjects, and correlation to the other instruments. The coefficient of variation (%CV) for instrument, positioning, interobserver, and short-term precision of the five calcaneal instruments ranged from 1.34-7.76%, 1.63-7.00%, 1.84-9.44%, and 1.99-7.04%, respectively. The %CVs for positioning, interobserver, and short- term precision were similar for calcaneal DEXA, calcaneal SEXA, and stiffness (as measured by Achilles). The %CVs for instrument precision were similar between calcaneal DEXA and SEXA. The ability of the five calcaneal instruments to discriminate osteoporotic from young normal subjects was similar based on the analysis of area under the receiver operating characteristic curves (range 0.88-0.93) and equivalent to DEXA of the calcaneus and hip (0.88-0.93). The correlations between the measurements of five calcaneal instruments were strong (0.80 ≤ r ≤ 0.91, p <0.001). These data suggest that although the precision is variable, the calcaneal QUS and SEXA instruments can discriminate between osteoporotic patients and young normal controls and appear to be a useful technique for assessment of osteoporosis.