BACKGROUND AND OBJECTIVES: There have been reports of an association between osteoprotegerin (OPG) and cardiovascular disease. Therefore, the aims of this study were to evaluate the association between the plasma OPG level and the severity of atherosclerosis, as well as search for conventional cardiovascular risk factors associated with the plasma OPG level in patients with coronary artery disease (CAD). SUBJECTS AND METHODS: Plasma OPG levels were measured in 583 consecutive patients (mean age: 62+/-10 yrs, M:F=398:185), using an ELISA method, with CAD confirmed from the coronary angiogram. The intima media thickness (IMT) of the common carotid artery was also measured in 252 patients. RESULTS: The plasma OPG level was correlated with the IMT (r=0.184, p=0.003), with the median level found to be elevated in accordance with the severity of CAD (2704 in 1VD vs. 2914 in 2VD vs. 3046 pg/mL in 3VD, p=0.024). Median plasma OPG levels were significantly higher in female (3024 vs. 2828 pg/mL, p=0.003) and DM patients (3098 vs. 2711 pg/mL, p<0.001), and positively correlated with age (r=0.340, p<0.001) and the HbA1C level (r=0.102, p=0.035), but showed an inverse correlation with BMI (r=-0.199, p<0.001). No correlation was found between high sensitive C reactive protein (hs-CRP) and the plasma OPG level, and no relation was found between CRP and the severity of CAD or the IMT. From a multivariate logistic regression analysis, increasing age (odds ratio, 1.053 [95% confidence interval, 1.034-1.073]), DM (odds ratio 1.664 [95% confidence interval, 1.149-2.410]) and a BMI less than 25 kg/mm2 (odds ratio, 1.625 [95% confidence interval, 1.142-2.314]) were associated with the supramedian OPG level (2831 pg/mL). CONCLUSION: The plasma OPG level might be a biochemical marker of atherosclerosis, and is associated with cardiovascular risk factors, especially DM and age.