The relation between parental history of myocardial infarction (MI) and risk of coronary artery disease (CAD) was prospectively examined among 45,317 U.S. male health professionals who were free of diagnosed CAD, 40 to 75 years of age in 1986 and followed for 2 years. These men provided details of parental history of MI, including their parents' age at the first event, their personal history of hypertension, hypercholesterolemia and diabetes mellitus, and a detailed dietary assessment completed at baseline. During 72,454 person-years of follow-up, 181 non-fatal MIs were documented, 49 men died from MI or sudden death, and 140 underwent coronary artery surgery or angioplasty. Compared with men without any history of parental MI, those whose mothers or fathers had had an MI at less than 70 years of age had a substantially elevated risk of MI (relative risk = 2.2, 95% confidence interval, 1.2 to 3.8 for maternal history; relative risk = 1.7, 95% confidence interval 1.2 to 2.3 for paternal history). Risk of MI increased with decreasing age at parental MI. Paternal but not maternal history of MI was related to increased risk of coronary artery surgery. These associations were not appreciably altered by controlling for diet or established risk factors, either individually or in multivariate models. These prospective data indicate that a history of MI in either parent is associated with an increased risk of CAD among men.