Introduction: Poly-vascular disease (PVD), defined as presence of atherosclerotic disease in >1 vascular territory, typically coronary artery disease (CAD), peripheral arterial disease (PAD), or cerebrovascular disease, is associated with worse CV prognosis. The impact of social vulnerability among this very high-risk subgroup has not been well studied. We aim to leverage readily available measures of neighborhood-level social vulnerability (area deprivation index, ADI) associated with increasing burden of overall and premature (<65 years) PVD in a large integrated healthcare system. Methods: Cross-sectional study using data from 1.12M patients aged 18+ years in Houston Methodist CVD Learning Health System Registry (2016-2022). Patients were ranked by ADI quintiles (Q1-Q5) as validated index of neighborhood socioeconomic disadvantage built from 17 metrics at census tract level quantified using Geographic Information Systems. CAD, PAD, and stroke were identified using ICD 10-CM codes. Results: We included a total of 1.1M adults with ADI ranking. Overall, prevalence of CAD, PAD and stroke was 5.7%, 1.7% and 3.2% respectively with 1.4% & 0.3% having vascular disease in 2 and 3 vascular beds respectively. Age-adjusted prevalence of any & premature PVD was higher with worse ADI groups ( Table ). Overall, 35% and 41% of patients with premature 2-3 PVD were in the highest 4-5 th ADI quintile (most deprived neighborhood) compared to 28% with premature single vascular CVD. After adjusting for age, sex, race/ethnicity, CV risk factors, adults in the highest ADI quintile had odds of 1.18(1.11-1.26) of PVD in 2 territories & 1.33(1.15-1.54) in 3 vascular beds compared to ADI quintile 1 (least deprived neighborhood). Conclusion: Readily available neighborhood social deprivation such as ADI is strongly associated with worsening poly-vascular CVD. It can be used to inform comprehensive preventive and management strategies for this vulnerable population at health system level.