Objectives. This study sought to determine whether nutrient-rich whole grains reduce mortality risk. Methods. The study included 38 740 Iowa women, aged 55 to 69 years. A food frequency questionnaire was used to obtain data on grain intake. Results. Median whole grain intake quintiles ranged from a median of 0.2 to more than 3 servings per day. Women with higher intakes had healthier lifestyles and less baseline disease. The total death rate decreased in increasing quintiles, and the pattern repeated for cancer, cardiovascular disease, and and other causes combined. Adjusted for lifestyle and baseline disease, the relative hazard rate ratio for total death was about 0.85 in daily consumers of whole grain. Findings persisted in strata of baseline healthy and diseased and were not explained by dietary fiber. Rates of total mortality, but not cardiovascular disease mortality, were higher among frequent consumers of refined grain. Conclusions. Total mortality risk was inversely associated with whole grain intake and positively associated with refined grain intake. Refined grains contributed more than 20% of energy intake, and whole grains contributed 1%. Substitution of whole for refined grain may reduce chronic disease risk in the United States.