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Background: The impact of marital status on cardiovascular disease (CVD) remains controversial in the general population. Aim: The present investigation sought to delineate the association between marital status and long-term major non-fatal and fatal CVD, along with all-cause mortality within the scope of the RIFLE project (Risk Factors and Life Expectancy). Methods: We examined the incidences of CVD, including cerebrovascular accidents and coronary heart disease (CHD), as well as all-cause mortality. In total, 47,167 individuals (46% female, average age 50 ± 9 years) were included in the analysis. Marital status at inception was categorized into married (inclusive of married or cohabitating) versus unmarried cohorts (including widowed, separated, divorced, or single individuals). Results: Compared to their married counterparts, unmarried subjects demonstrated a heightened risk for CVD in both females and males. Throughout a median follow-up span of 7.4 years (interquartile range from 6 to 9 years), married participants, adjusting for standard risk factors, exhibited reduced mortality rates attributed to CHD [hazard ratio (HR) 0.54 (95% confidence interval (CI) 0.33–0.86)) and all causes (HR 0.75 (95% CI 0.62–0.91)] within the aggregate population; this reduction persisted for both CHD-specific [HR 0.39 (95% CI 0.51–0.90)]and all-cause mortality [HR 0.68 (95% CI 0.51–0.90)], independent of traditional risk factors in women. No associations were evident between matrimonial status and any measured outcomes in males. Conclusions: Within primary care settings, marital status should be considered a potential correlate of long-term CHD and overall mortality risks, especially among women. [ABSTRACT FROM AUTHOR]