Background Previous models used to predict individual risk of death from coronary heart disease (CHD) were developed from data of 3 decades ago from the Framingham Heart Study. CHD mortality rates have declined markedly since that period as a result of improvement in both risk factor status and medical interventions. Generalization of the results from this one study to the population at large remains a matter of concern. We compared predictive functions derived from the major risk factors for CHD from Framingham and 2 more recent national cohorts, the First and Second National Health and Nutrition Examination Survey (NHANES I and NHANES II). Methods and Results The participants included 1846 men and 2323 women 35 to 69 years of age and free of CHD at the fourth examination (1954 to 1958) from the Framingham Study; 2753 men and 3858 women from the NHANES I (1971 to 1975); and 2655 men and 3050 women from NHANES II (1976 to 1980). The 3 cohorts were monitored for 24, 20, and 15 years, respectively. Significant heterogeneity existed among studies in the magnitude of the Cox coefficients for the individual factors (ie, age, systolic blood pressure, serum total cholesterol, and smoking status), especially among men. When risk factors were considered collectively, however, functions derived from and applied to different cohorts had a similar ability to rank individual risk. The areas under the receiver operating characteristic curves were 0.71 to 0.76 in men and 0.76 to 0.81 in women when different risk functions were applied to their own population or to a second population. The cumulative CHD survival observed in women in the 2 national cohorts was close to what was predicted from the Framingham equation. However, Framingham overestimated the cumulative CHD mortality rates in men in NHANES I and NHANES II. Conclusions The Framingham risk model for the prediction of CHD mortality rates provides a reasonable rank ordering of risk for individuals in the US white population for the period 1975 to 1990. However, prediction of absolute risk is less accurate. (Am Heart J 1999;137:837-45.)