Myocardial infarction in the young provides a unique model for the investigation of potential interactions between atherosclerotic and prothrombotic risk factors. Because myocardial infarction reflects atherothrombotic disease, it is important to take into account factors related to atherosclerosis when examining prothrombotic factors as potential determinants of myocardial infarction. In Western societies, there are increases in both the prevalences of metabolic risk factors and atherosclerotic coronary disease with aging. The clinical expression of the thrombotic risk associated with heritable factors, such as factor V Leiden, as myocardial infarction appears to occur only in the presence of other risk factors, such as smoking and known metabolic risk factors related to atherosclerosis. If confirmed in other studies of factor V Leiden and with other mutations related to prothrombotic risk, these observations will likely have both etiologic and practical consequences. Finally, we suggest that efforts to determine whether a prothrombotic risk factor contributes "independently" to the risk of myocardial infarction may lead to a significant underestimation of the importance of the factor in the occurrence of myocardial infarction, particularly among clinically-important subsets of the population.