In addition to the inverse association of dietary lycopene with various cancers, studies suggest a role for lycopene in cardiovascular disease (CVD) prevention. We determined whether the intake of lycopene or tomato-based foods is associated with the risk of CVD in a prospective cohort of 39,876 middle-aged and older women initially free of CVD and cancer. Participants completed a food-frequency questionnaire and provided self-reports of coronary risk factors. Dietary lycopene levels were divided into quintiles, and primary lycopene food sources (total tomato-based products, including tomatoes, tomato juice, tomato sauce and pizza) were categorized. During 7.2 y of follow-up, 719 CVD cases (including myocardial infarction, stroke, revascularization and CVD death) occurred. Compared with women in the 1st quintile of lycopene, those in increasing quintiles had multivariate relative risks (RR) of CVD of 1.11, 1.14, 1.15 and 0.90 (P for trend = 0.34). For the consumption of tomato-based products, women consuming 1.5 to <4, 4 to <7, 7 to <10 and >or=10 servings/wk had RR (95% CI) of CVD of 1.02 (0.82-1.26), 1.04 (0.82-1.31), 0.68 (0.49-0.96) and 0.71 (0.42-1.17) (P for trend = 0.029) compared with women consuming <1.5 servings/wk. Among lycopene food sources, those in the highest levels of tomato sauce (>or=2 servings/wk) and pizza intake (>or=2 servings/wk), with multivariate RR of 0.76 (0.55-1.05) and 0.66 (0.37-1.18), respectively, had potential reductions in CVD risk. Dietary lycopene was not strongly associated with the risk of CVD. However, the possible inverse associations noted for higher levels of tomato-based products, particularly tomato sauce and pizza, with CVD suggest that dietary lycopene or other phytochemicals consumed as oil-based tomato products confer cardiovascular benefits.