Introduction: Understanding the progression of cardiovascular multimorbidity and recognizing differences are needed to develop effective strategies to improve health outcomes. There is a knowledge gap in the potential unequal burden and progression of cardiovascular multimorbidity. Our objective is to investigate sex differences in the progression of cardiovascular multimorbidity among older adults in the US and estimate relative life expectancies among patients with severe multimorbidity. Hypothesis: We hypothesized that life expectancy among older adults with severe cardiovascular multimorbidity is inversely related to the number of comorbid conditions and progresses more acutely in males. Methods: Repeated cross-sectional cohort study of inpatient, outpatient, and carrier claims for a 5% nationwide Medicare sample. We included Medicare beneficiaries aged 65 or older enrolled in Medicare Fee-For-Service program from 2010 to 2020 and living in the continental US. Multistate life table models were employed to estimate cardiovascular disease (CVD) progression and total life expectancies from ages 65 to 85 years. Progression probabilities and life expectancies were adjusted for age, non-cardiovascular comorbidities, and Medicaid dual eligibility. A microsimulation approach was utilized to derive life tables, and bootstrapping was used to estimate variability. The primary outcome was the development and progression of cardiovascular multimorbidity, defined by the number of major cardiovascular conditions (atrial fibrillation, acute myocardial infarction, heart failure, stroke, and chronic ischemic heart disease). Comorbidities were assessed using validated algorithms based on diagnostic codes billed over a 1-year lookback period, and beneficiaries were followed forward from their index date. Results: Of 2,189,633 beneficiaries, the median age was 69, median follow-up was 5 years, and 55.9% were female. For male beneficiaries, odds of developing cardiovascular comorbidities were significantly higher than for females, with odds ratios ranging from 1.20 (95% CI 1.19-1.21) for one CVD to 1.97 (95% CI 1.88-2.06) for 1 or more of the 4 CVD comorbidities. Men with 1 CVD at baseline had significant odds of developing 2 (OR: 1.10, 95% CI 1.09-1.11) and four CVDs (OR: 1.29, 95% CI 1.24-1.34), as well as a significant mortality risk (OR: 1.19, 95% CI 1.18-1.21). However, for men with 4 CVDs, the odds of progressing to 5 were not significant (OR: 1.00, 95% CI 0.97-1.04). Across levels of baseline multimorbidity, male beneficiaries had significantly elevated mortality risks compared to females, with the highest risk for those with no baseline CVD (OR: 1.50, 95% CI 1.48-1.52). Conclusions: These findings suggest persistent sex differences in cardiovascular multimorbidity progression, identifying a potentially important target for the improvement of health outcomes.