Using data from the Framingham Heart Study, the authors examined lifetime risk for coronary heart disease (CHD) by cholesterol levels for men and women at selected ages. At all ages, there was a 1.5- to 2-fold greater lifetime risk for CHD in subjects with total cholesterol (TC) level of 240 mg/dL or greater (≥6.20 mmol/L) vs less than 200 mg/dL (<5.20 mmol/L). At age 40 years, the lifetime risks for CHD through age 80 years for men with TC level 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 (≥6.20 mmol/L) were 31%, 43%, and 57%, respectively; 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 for CHD were 3%, 5%, and 12% for men and 1%, 2%, and 5% for women, respectively. Lifetime risk was also stratified well by cholesterol subfractions that included high-density lipoprotein cholesterol. These data support routine cholesterol screening in younger patients, who may have low short-term but high lifetime risks for CHD, and they may help target high-risk patients for lifestyle modification or drug therapy.