The Framingham risk score (FRS) is widely used in clinical practice to identify subjects at high risk for developing coronary heart disease. However, FRS may not accurately identify subjects at risk. We measured subclinical atherosclerosis in the coronary arteries and aorta with the presence of calcium and in the common carotid artery by intima-media thickness in 498 healthy subjects. The distribution of these subclinical atherosclerosis measures was evaluated across 3 strata of the FRS. Coronary arteries with the presence of calcium, aorta with the presence of calcium, and carotid artery by intima-media thickness were significantly independently associated with FRS. The FRS increased with the number of arterial sites with atherosclerosis; 69% of the subjects categorized in the low risk group (FRS <10%), 95% of the intermediate risk group (FRS 10% to 20%), and 100% of the high risk group (FRS >20%) had > or = 1 vascular imaging studies demonstrating subclinical atherosclerosis. In the low risk group, subjects with atherosclerosis had a longer history of lifetime smoking compared with those without atherosclerosis. In conclusion, subclinical atherosclerosis is prominent across the spectrum of FRS. Evaluation of subclinical atherosclerosis in different arterial sites in addition to FRS may be useful in targeting subjects for lifestyle and other interventions.