The objective of this study was to assess the associations and population attributable risks (PAR) of risk factor combinations and ischemic heart disease (IHD) mortality in the United States. We used logistic regression models to assess the association of risk factors with IHD in the First National Health and Nutrition Examination Survey (1971-1974) and Epidemiologic Follow-up Study (1982-1992) among white and black men and women. We examined eight modifiable risk factors: hypertension, elevated serum cholesterol, diabetes, overweight, current smoking, physical inactivity, depression, and nonuse of replacement hormones. Risk factors associated with IHD mortality were the same among white and black men (i.e., age, education, smoking, diabetes, hypertension, and serum cholesterol). Age, education, smoking, diabetes, and hypertension were the risk factors among white and black women. Physical inactivity, nonuse of replacement hormones, serum cholesterol, and overweight were the additional risk factors among white women. Adjusted for demographic risk factors, overall PARs for study risk factors were 41.2% for white men, 60.5% for white women (with five risk factors only), 49.2% for black men, and 71.2% for black women. Much IHD mortality attributable to individual risk factors is caused by those factors in combination with other risk factors; relatively little mortality is attributable to each risk factor in isolation. Analysis that does not examine risk factor combinations may greatly overestimate PARs associated with individual risk factors.