Family history of myocardial infarction (FHMI) is an independent risk factor for cardiovascular (CV) events but may be more informative in certain subgroups. The association between FHMI and the presence of coronary artery calcium (CAC) was examined in various age and risk factor groups in the Dallas Heart Study (DHS), a population-based probability sample of subjects aged 30 to 65 years. Analyses were stratified by age (with the young group composed of men aged <45 years and women aged <55 years) and by the presence of 0, 1, 2, or >2 CV risk factors. In the overall cohort of 2,743 subjects, FHMI was an independent predictor of CAC (adjusted odds ratio 1.3, 95% confidence interval 1.1 to 1.7), attributable to an independent association between FHMI and CAC in the young group (adjusted odds ratio 1.5, 95% confidence interval 1.0 to 2.1) that was not evident in the older subset (adjusted odds ratio 1.2, 95% confidence interval 0.91 to 1.6, interaction p = 0.02). In the young cohort, the association between FHMI and CAC was particularly robust in those with ≥2 risk factors (FHMI–by–risk factor interaction p = 0.04). In older subjects, FHMI was not associated with CAC for any risk factor category (p >0.05 for each). In conclusion, this study suggests that FHMI is a more important predictor of atherosclerosis in young compared with older adults and, among the young, in those with multiple CV risk factors.