The aim was to investigate psychological risk profiles of cardiovascular disease (CVD). Depression and anxiety have been linked to CVD, but research has not incorporated personality and sex-specific analyses are warranted. In this study, we examine the role of sex, neuroticism, extraversion, anxiety and depression on the risk of CVD.Using data from the HUNT-study and the mortality register, 32,383 (57.10% men) participants were followed for an average of 10.48 years. During this time, 142 died of myocardial infarction (MI) and 111 of stroke.Cox regression showed that depression (HR = 1.07, 95% CI = [1.00, 1.14]) and neuroticism (1.23 [1.08, 1.40]) were significantly related to an increased risk of MI. One standard unit increase in depression and neuroticism was associated with 1.22 [CI 1.01, 1.47] increase and 1.43 [CI 1.14, 0.78] increase in the risk of MI respectively. For stroke, there was no significant effect of anxiety, depression or personality. However, we found a significant interaction effect between sex and extraversion where higher extraversion was associated with greater risk of stroke for women only.Both neuroticism and depression were related to MI. We observed an interaction between extraversion and sex with stroke, but the effect size was small. The role of extroversion as a risk factor for CVD remains inconclusive.