Many studies have suggested that hormone replacement therapy reduces the risk of coronary heart disease. Electron beam tomography is a highly sensitive noninvasive method by which to detect coronary artery disease. Our objective was to investigate whether hormone replacement therapy had an effect on coronary artery disease as determined by electron beam tomography in postmenopausal women. Nine hundred fourteen self-referred postmenopausal women older than 50 years underwent electron beam tomography. Each woman completed a questionnaire regarding age, risk factors, menopausal status, and hormone replacement therapy. Women taking hormone replacement therapy were slightly younger (57.8 years) than those not (60.7 years). A significantly higher incidence of a family history of myocardial infarction and smoking history was found in the group taking hormone replacement therapy, whereas more diabetics were in the group not taking hormone replacement therapy. The mean total coronary artery scores for women receiving hormone replacement therapy and not receiving hormone replacement therapy were 54.2 and 86.2, respectively (p = 0.02). Independent predictive variables of a positive coronary artery calcium score with multiple logistic regression analysis were age, hypercholesterolemia, diabetes, and estrogen use. These results suggest that hormone replacement therapy is associated with less coronary artery disease in postmenopausal women as determined by electron beam tomography.