Evidence for cardioprotective effects of lycopene is inconsistent. Studies of circulating lycopene generally report inverse associations with CVD risk, but studies based on lycopene intake do not. The failure of dietary studies to support the findings based on biomarkers may be due in part to misclassification of lycopene intakes. To address this potential misclassification, we used repeated measures of intake obtained over 10 years to characterise the relationship between lycopene intake and the incidence of CVD (n 314), CHD (n 171) and stroke (n 99) in the Framingham Offspring Study. Hazard ratios (HR) for incident outcomes were derived from Cox proportional hazards regression models using logarithmically transformed lycopene intake adjusted for CVD risk factors and correlates of lycopene intake. HR were interpreted as the increased risk for a 2·7-fold difference in lycopene intake, a difference approximately equal to its interquartile range. Using an average of three intake measures with a 9-year follow-up, lycopene intake was inversely associated with CVD incidence (HR 0·83, 95% CI 0·70, 0·98). Using an average of two intake measures and 11 years of follow-up, lycopene intake was inversely associated with CHD incidence (HR 0·74, 95% CI 0·58, 0·94). Lycopene intake was unrelated to stroke incidence. The present study of lycopene intake and CVD provides supporting evidence for an inverse association between lycopene and CVD risk; however, additional research is needed to determine whether lycopene or other components of tomatoes, the major dietary source of lycopene, are responsible for the observed association.