BACKGROUND: Most data linking chronic stress with cardiovascular disease (CVD) risk factors and outcomes have focused on single-domain stress measurements. We evaluated the association between a novel composite measure of chronic perceived stress and CVD risk factors and outcomes in a diverse population. METHODS AND RESULTS: Individual chronic stress subcomponents (generalized stress, psychosocial, financial, and neighborhood stress) were standardized and integrated to create a novel composite stress score (CSS). Participants from the DHS (Dallas Heart Study) phase 2 (2007-2009) visit without prevalent CVD who completed chronic stress questionnaires were included (n=2685). Associations between CSS and demographics, cardiac risk factors, and health behaviors were assessed in multivariable analyses. Cox proportional hazards models adjusting for traditional risk factors were used to determine associations of the CSS with adjudicated atherosclerotic CVD and global CVD (atherosclerotic CVD, heart failure, and atrial fibrillation) outcomes. CSS was higher among participants who were younger, women, and Black or Hispanic individuals, with lower income and educational attainment ( CONCLUSIONS: Composite measures of chronic stress are higher in vulnerable populations and may help identify individuals at risk for CVD who may benefit from enhanced prevention strategies.