Background: Adherence to the Dietary Guidelines for Americans, measured with the US Department of Agriculture Healthy Eating Index (HEI), was associated with only a small reduction in major chronic disease risk. Research suggests that greater reductions in risk are possible with more specific guidance.

Objective: We evaluated whether 2 alternate measures of diet quality, the Alternate Healthy Eating Index (AHEI) and the Recommended Food Score (RFS), would predict chronic disease risk reduction more effectively than did the HEI.

Design: A total of 38 615 men from the Health Professional's Follow-up Study and 67 271 women from the Nurses' Health Study completed dietary questionnaires. Major chronic disease was defined as the initial occurrence of cardiovascular disease (CVD), cancer, or nontraumatic death during 8-12 y of follow-up.

Results: High AHEI scores were associated with significant reductions in risk of major chronic disease in men [multivariate relative risk (RR): 0.80; 95% CI: 0.71, 0.91] and in women (RR: 0.89; 95% CI: 0.82, 0.96) when comparing the highest and lowest quintiles. Reductions in risk were particularly strong for CVD in men (RR: 0.61; 95% CI: 0.49, 0.75) and in women (RR: 0.72; 95% CI: 0.60, 0.86). In men but not in women, the RFS predicted risk of major chronic disease (RR: 0.93; 95% CI: 0.83, 1.04) and CVD (RR: 0.77; 95% CI: 0.64, 0.93).

Conclusions: The AHEI predicted chronic disease risk better than did the RFS (or the HEI, in our previous research) primarily because of a strong inverse association with CVD. Dietary guidelines can be improved by providing more specific and comprehensive advice.