Abstract Introduction Erectile dysfunction can be a harbinger of underlying cardiovascular (CVD) risk factors in men. Despite the higher prevalence of sexual dysfunction among women than men, the association between vascular impairment and female sexual dysfunction (FSD) as well as the pathophysiology of FSD remains understudied. Objective Our objective was to assess the association of FSD with major adverse cardiac events (MACE) using a large claims database. Methods A US-based claims database network (TriNetX Diamond Network) was queried from 2009 to 2022 to create our cohorts. Our study cohort included adult (age 18+) females diagnosed with FSD (ICD-10 F52) excluding those with heart failure (I50) or unstable angina (I20.0). Our control cohort excluded females diagnosed with FSD, heart failure, or unstable angina. Propensity-matching between the cohorts for age, ethnicity, race, BMI, family history of CVD (Z82.4), tobacco usage (Z72.0), type 2 diabetes (E11), hyperlipidemia (E78), hypertension (I10), and utilization of inpatient (1013659), outpatient (1013626), or emergency services (1013711) was conducted. MACE was defined as heart attack (I21, I22), stroke (I60, I61, I62, I63), or death within five years of FSD diagnosis. A sub-analysis by age (18-40 years, 41-55 years, and >55 years) was conducted. Amongst the >55 years cohort, the effect of ≥3 vaginal estrogen prescriptions on MACE was evaluated. Results All results are reported for our study cohorts in comparison to an equivalent number of propensity-matched controls. Adult females diagnosed with FSD (n=65,265) had significantly lower odds of heart attack (odds ratio (OR) 0.26 [95% CI 0.22 – 0.30]), stroke (OR 0.29 [0.26 – 0.32]), death (OR 0.46 [0.41 – 0.51]), and any MACE event (OR 0.32 [0.30 – 0.34]) (Table 1). This trend remained in females aged 18-40 years (n=18,473) and diagnosed with FSD (Table 2); they had significantly lower odds of heart attack (OR 0.31 [0.16 – 0.59]), stroke (OR 0.27 [0.18 – 0.39]), death (OR 0.36 [0.21 – 0.63]), and any MACE event (OR 0.30 [0.22, 0.39]). Among 41–55-year-olds (n=21,648) with FSD, (Table 2) we found our study cohort to have significantly lower odds of heart attack (OR 0.21 [0.15 – 0.29]), stroke (OR 0.26 [0.22 – 0.32]), death (OR 0.39 [0.30 – 0.50]), and any MACE event (OR 0.28 [0.24 – 0.32]) (Table 2). Finally, the population of individuals aged > 55 years (n=25,144) were found to have significantly lower odds of heart attack (OR 0.30 [0.25 – 0.36]), stroke (OR 0.35 [0.31 – 0.39]), death (OR 0.54 [0.47 – 0.62]), and any MACE event (OR 0.38 [0.36 – 0.42]). There was no difference in the odds of MACE event by vaginal estrogen usage in this age-group (OR 0.66 [0.31 – 1.38]). Conclusions In this large claims-based analysis, we demonstrated that females diagnosed with FSD had lower odds of MACE. Though screening for CV risk should be discussed with all patients, our results suggest that vascular impairment may not have a role in the pathophysiology of FSD. Disclosure No