We examined whether personality traits are differently associated with coronary heart disease and stroke mortality. Participants were pooled from three prospective cohort studies (Health and Retirement Study, Wisconsin Longitudinal Study graduate and sibling samples; n = 24,543 men and women, mean age 61.4 years, mortality follow-up between 3 and 15 years). There were 423 coronary heart disease deaths and 88 stroke deaths during 212,542 person-years at risk. Higher extraversion was associated with an increased risk of stroke (hazard ratio per each standard deviation increase in personality trait HR = 1.41, 95 % CI 1.10-1.80) but not with coronary heart disease mortality (HR = 0.93, 0.83-1.05). High neuroticism, in turn, was more strongly related to the risk of coronary heart disease (HR = 1.16, 1.04-1.29) than stroke deaths (HR = 0.95, 0.78-1.17). High conscientiousness was associated with lower mortality risk from both coronary heart disease (HR = 0.74, 0.67-0.81) and stroke (HR = 0.78, 0.63-0.97). Cardiovascular risk associated with personality traits appears to vary between main cardiac and cerebral disease endpoints.