Background: Adults experiencing homelessness experience 40-50% greater mortality risk from heart disease than the general population. Research has identified several risk factors, including poor glycemic, hypertension, and hyperlipidemia control, high prevalence of cigarette smoking, and elevated homocysteine levels from smoking and poor nutrition. Implemented in 2014, the Vulnerability Index - Service Prioritization Decision Assistance Tool (VI-SPDAT v1) is a 50 question survey intended to proscribe appropriate levels of intervention, and prioritize the waiting list for housing services. Method: The VI-SPDAT was used to assess a cohort of individuals experiencing homelessness (n=4,739 unique participants) seeking subsidized housing services in a single county in Texas. The results of the self-report survey’s medical questions were validated through linkage to the community’s Health Information Exchange (HIE) for indigent populations. Confirmatory Factor Analysis tests were performed on all first-time assessments, and modification indices were used to optimize a 5 factor model of global vulnerability in the homeless population. Logistic regression was used to identify independent covariates associated with reported heart disease within various sections (explicit domains) within the measure. Results: One quarter of all individuals assessed with the VI-SPDAT reported a history of heart disease or arrhythmia (24.98%). Criterion validation of the tool using HIE data supported that this prevalence estimate was possibly even under-reported, with diagnostic data available for 3,240 participants and a 38.67% prevalence of heart disease or arrhythmia (26.44%, adjusted for full sample). Rates of the condition were elevated for females (27.5% vs 24.0%), non-Hispanic participants (25.7% vs 21.7%), and those experiencing chronic homelessness (HUD definition; 26.8% vs 22.5%). Behavioral and cognitive health conditions associated with heart disease included problems with concentration, history of traumatic brain injury, ED visits for mental health symptom management, and poor medication adherence (all p<0.001). Social risk factors such as being the victim of an attack, associating with perceived bad influences, having people they don’t like in their lives, and being forced or tricked into doing things by others were all associated with heart disease (all p<0.001). Discussion: This research presents a rare window into the complex interrelationships of social and medical vulnerability that surround cardiovascular diseases in a sample of extremely vulnerable individuals. Analytical techniques applied to this data show several relationships not previously explored in the literature, and support the existing evidence of heightened cardiovascular risk due to multiple exposures more common in those experiencing homelessness.