OBJECTIVE: The purpose of this study is to examine whether mental vulnerability is a risk factor for the development of ischemic heart disease (IHD) after adjustment for well-established risk factors. METHODS: In three prospective cohort studies in Copenhagen County, Denmark, we recorded the level of mental vulnerability and possible risk factors to IHD at baseline. For follow-up, the sample was linked to relevant registries to identify all cases of fatal and nonfatal IHD. The relationship between mental vulnerability and IHD was examined using both Kaplan-Meir and Cox proportional hazard models adjusting for possible confounding factors. RESULTS: Mental vulnerability was significantly associated with the risk for IHD (medium mental vulnerability: hazard ratio 1.41, 95% confidence interval 1.04-1.91; and high mental vulnerability: hazard ratio 2.05; 95% confidence interval 1.46-2.88), after adjusting for confounders. CONCLUSION: Our results imply that mental vulnerability is an independent risk factor for IHD.