Low bone mineral density (BMD) and coronary artery disease (CAD) share common risk factors. To investigate whether low BMD (osteoporosis and/or osteopenia) independently predicts CAD compared with traditional cardiovascular risk factors, a retrospective analysis was performed in consecutive ambulatory patients (n = 209, 89% women) who underwent dual-energy x-ray absorptiometry and coronary angiography within the same 12-month period. Angiograms were classified as showing significant CAD if > or =50% luminal narrowing in a major coronary artery was noted. Clinical variables associated with CAD (age, hypertension, diabetes, high fasting glucose level, smoking, family history of CAD, and dyslipidemia) were examined. Dual-energy x-ray absorptiometric scans were classified based on World Health Organization criteria: normal (T score >-1.0 SD), osteopenia (T score -1.0 to -2.5 SD), and osteoporosis (T score <-2.5 SD). Univariate and multivariate analyses were employed to determine whether low BMD independently predicts CAD. Univariate predictors of CAD were hypertension, smoking, diabetes, high fasting glucose level, dyslipidemia, family history of CAD, and low BMD. Multivariate predictors were hypertension, family history of CAD, fasting glucose level, and osteoporosis. Odds ratio for the prediction of angiographically documented CAD was highest for osteoporosis (odds ratio 5.6, 95% confidence interval 2.6 to 12.0, p <0.0001). In conclusion, low BMD appears to independently predict significant CAD in women, with a higher odds ratio than traditional risk factors. Our study is the first to report osteoporosis as a predictor of angiographically proved CAD in a population predominantly of women.