We sought to assess how cholesterol levels at different ages modify the remaining lifetime risk of coronary heart disease (CHD). We included all Framingham Heart Study participants examined from 1971 through 1996 who did not have CHD and were not receiving lipid-lowering therapy. At index ages of 40, 50, 60, 70, and 80 years, participants were stratified by total cholesterol level and by cholesterol subfractions. Lifetime risk of CHD was calculated with death free of CHD as a competing event. Among 3269 men and 4019 women, 1120 developed CHD and 1365 died free of CHD during follow-up. At each index age, lifetime risk of CHD increased with higher cholesterol levels, and time to event decreased. At age 40 years, the lifetime risks of CHD through age 80 years for men with total cholesterol levels less than 200 mg/dL (<5.20 mmol/L), 200 to 239 mg/dL (5.20-6.19 mmol/L), and 240 mg/dL or greater (> or =6.20 mmol/L), respectively, were 31%, 43%, and 57%; for women, the lifetime risks were 15%, 26%, and 33%, respectively. Lifetime risks contrasted sharply with shorter-term risks: at age 40 years, the 10-year cumulative risks of CHD were 3%, 5%, and 12% for men, and 1%, 2%, and 5% for women, respectively. Lifetime risk of CHD increases sharply with higher total cholesterol levels for men and women at all ages. These data support an important role for cholesterol screening in younger patients, and they may help target high-risk patients for lifestyle modification or drug therapy.