Background: Studies of fruit and vegetable consumption in relation to overall health are limited. We evaluated the relationship between fruit and vegetable intake and the incidence of cardiovascular disease and cancer and of deaths from other causes in two prospective cohorts. Methods: A total of 71 910 female participants in the Nurses' Health study and 37 725 male participants in the Health Professionals' Follow-up Study who were free of major chronic disease completed baseline semiquantitative food-frequency questionnaires in 1984 and 1986, respectively. Dietary information was updated in 1986, 1990, and 1994 for women and in 1990 and 1994 for men. Participants were followed up for incidence of cardiovascular disease, cancer, or death through May 1998 (women) and January 1998 (men). Multivariable-adjusted relative risks were calculated with Cox proportional hazards analysis. Results: We ascertained 9329 events (1964 cardiovascular, 6584 cancer, and 781 other deaths) in women and 4957 events (1670 cardiovascular diseases, 2500 cancers, and 787 other deaths) in men during follow-up. For men and women combined, participants in the highest quintile of total fruit and vegetable intake had a relative risk for major chronic disease of 0.95 (95% confidence interval [CI] = 0.89 to 1.01) times that of those in the lowest. Total fruit and vegetable intake was inversely associated with risk of cardiovascular disease but not with overall cancer incidence, with relative risk for an increment of five servings daily of 0.88 (95% CI = 0.81 to 0.95) for cardiovascular disease and 1.00 (95% CI = 0.95 to 1.05) for cancer. Of the food groups analyzed, green leafy vegetable intake showed the strongest inverse association with major chronic disease and cardiovascular disease. For an increment of one serving per day of green leafy vegetables, relative risks were 0.95 (95% CI = 0.92 to 0.99) for major chronic disease and 0.89 (95% CI = 0.83 to 0.96) for cardiovascular disease. Conclusions: Increased fruit and vegetable consumption was associated with a modest although not statistically significant reduction in the development of major chronic disease. The benefits appeared to be primarily for cardiovascular disease and not for cancer.