OBJECTIVE: The purpose of the study was to assess the risk of CHD associated with excess weight measured by BMI and waist circumference (WC) in two large cohorts of men and women. DESIGN, SETTING, SUBJECTS: Participants in two prospective cohort studies, the Health Professionals Follow-up Study (N = 27,859 men; age range 39-75 years) and the Nurses' Health Study (N = 41,534 women; 39-65 years) underwent 16-year follow-up through 2004. RESULTS: 1,823 incident cases of CHD among men and 1,173 cases among women were documented. Compared to men with BMI 18.5 to 22.9 kg/m2, those with a BMI > 30.0 kg/m2 had a multivariate-adjusted RR of CHD of 1.81 (95% CI 1.48 - 2.22). Among women, those with a BMI > 30.0 kg/m2 had a RR of CHD of 2.16 (95% CI 1.81 - 2.58). Compared to men with a WC < 84.0 cm, those with WC of greater than 102.0 cm had a RR of 2.25 (95% CI 1.77 - 2.84). Among women, the RR of CHD was 2.75 (95% CI 2.20 - 3.45) for those with WC of greater than 88.0 cm. CONCLUSIONS: In these analyses from two large ongoing prospective cohort studies, both BMI and WC strongly predicted future risk of CHD. Furthermore, WC thresholds as low as 84.0 cm in men and 71.0 cm in women may be useful in identifying those at increased risk of developing CHD. The findings have broad implications in terms of CHD risk assessment in both clinical practice and epidemiologic studies.