Background—A family history of coronary heart disease (CHD) is an independent risk factor for cardiovascular events. However, the mechanisms underlying this susceptibility have not been fully elucidated. We hypothesized that an important mediator of the familial predisposition to CHD is subclinical atherosclerosis, which is detectable by noninvasive imaging.Methods and Results—We studied 1662 subjects (mean age 57, 51% women) in the Framingham Offspring Study who underwent carotid ultrasonography and had both biological parents in the original (parental) cohort. Parental CHD events were validated prospectively by a physician endpoint committee. The associations of carotid intima-media thickness (IMT) with premature parental CHD (occurring before age 60) and any parental CHD (no age restriction) were examined in age- and multivariable-adjusted analyses. Age-adjusted mean internal carotid IMT was higher in subjects who had at least one parent with premature CHD than in those without a validated parental history of premature CHD (men 1.13 versus 1.04 mm,P<0.01; women 0.92 versus 0.85 mm,P=0.03). In both sexes, these differences remained significant after adjustment for cardiovascular risk factors. In analyses without a restriction on parental age of CHD onset, the association between carotid IMT and parental CHD was not statistically significant. There was also no significant association of common carotid IMT with premature or any parental CHD.Conclusions—These findings suggest that subclinical atherosclerosis, assessed in the carotid arteries, is more prevalent in individuals with a family history of CHD. Early-onset parental CHD, in particular, identifies offspring with a strong familial predisposition to atherosclerosis.