The female advantage in coronary heart disease occurrence is not completely understood. To characterize gender differences in cardiovascular disease by vascular site, the authors compared degrees of coronary, carotid, peripheral, and aortic atherosclerosis in men and women aged>or=55 years from the population-based Rotterdam Study (Rotterdam, the Netherlands). Data were collected between 1997 and 2000. A subset of 2,013 participants had data on both coronary calcification and one or more measures of extracoronary atherosclerosis, including intima-media thickness (IMT), carotid plaques, ankle-arm index (AAI), and aortic calcification. The multivariable-adjusted male:female odds ratios for calcium score>1,000 were 7.8 (95% confidence interval (CI): 3.2, 19.3), 5.4 (95% CI: 2.8, 10.2), and 3.0 (95% CI: 1.7, 5.2) in the lowest, middle, and highest age tertiles, respectively. For IMT>1.0 mm, severe carotid plaques, AAI<0.90, and severe aortic calcification, ratios did not decline with age. Overall multivariable-adjusted male:female odds ratios for these measures were 2.9 (95% CI: 2.0, 4.1), 2.0 (95% CI: 1.4, 2.8), 0.9 (95% CI: 0.7, 1.3), and 1.0 (95% CI: 0.8, 1.5), respectively. The authors conclude that the gender difference in atherosclerosis is larger in the coronary vessels than in other vascular beds. Remarkably, it is absent in the aorta and the lower-extremity vessels. Factors causing this site-specific gender difference require further investigation.