The relation between caffeinated coffee consumption and heart disease morbidity and mortality is of great interest given the extensive use of this beverage. A recent prospective epidemiologic study found a strong protective association in elderly subjects without moderate to severe hypertension in the NHANES. To test this association in the Framingham Heart Study population, in which cardiovascular risk factors and health behaviors were carefully documented, Cox regression analyses were conducted for 1,354 subjects aged 65.4 to 96.6 years at study entry. There were 210 deaths from cardiovascular disease and 118 from coronary heart disease (CHD) during 10.1 years of follow-up. A significant negative association between caffeinated coffee consumption and CHD mortality was observed for subjects with systolic blood pressure (BP) <160 mm Hg and diastolic BP <100 mm Hg. The decrease in risk of CHD mortality for any caffeinated coffee versus none was 43% (95% confidence interval 9 to 64). This decreased risk appeared to be caused primarily by an inverse prospective relation between caffeinated coffee consumption and the development or progression of heart valve disease. The decrease in risk of heart valve disease for subjects with systolic BP <160 mm Hg and diastolic BP <100 mm Hg for any caffeinated coffee versus none was 43% (95% confidence interval 4 to 66). In conclusion, caffeinated coffee consumption was associated with lower risk of CHD mortality and heart valve disease development or progression in older Framingham subjects without moderate or severe hypertension.