Abstract Introduction: Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment for malignant and non-malignant hematologic diseases. However, long-term HCT survivors have a >4-fold risk of developing cardiovascular disease (CVD) compared to the general population, and CVD is a leading cause of excess mortality after HCT. Comorbidities that emerge after HCT such as hypertension (HTN), diabetes mellitus (DM), and dyslipidemia (DL) are important modifiers of CVD risk, but the impact of social determinants of health (SDOH) on the development of these risk factors and resultant CVD has not been well-characterized. Methods: This retrospective cohort study included 889 patients who underwent an allogenic HCT between 2013 and 2019 at City of Hope and survived ≥1y after HCT. Demographic, disease, treatment, comorbidity, and health outcomes data were abstracted from medical records. The social vulnerability index (SVI), obtained from the Center for Disease Control, represented overall social vulnerability and included 4 themes: socioeconomic status, household composition & disability, minority status & language, and housing & transportation. SVI scores were derived using patients’ addresses at time of HCT. SVI scores ranged from 0 (least vulnerable) to 100 (most vulnerable). Fine-Gray regression analysis evaluated the association between SVI and risk of HTN, DM, and DL, adjusted for age at HCT and treating death as competing risk. We also evaluated the association between having 0, 1, ≥2 cardiovascular risk factors on incidence of clinically significant CVD (heart failure, coronary artery disease, pericarditis, stroke, intracranial hemorrhage, arrhythmia, and/or valvular disease) after HCT. Results: Mean age at HCT was 44.2y (standard deviation 19.8y); 56.7% were male, 43.8% were non-Hispanic White, 35.4% were Hispanic, and 12.9% were Asian. The most common diagnosis was acute myeloid leukemia (39.6%); 48.6% received reduced intensity conditioning. Higher overall SVI was associated with increased risk of HTN (adjusted Hazard Ratio per 10 unit increase in SVI [aHR] 1.10, 95%CI 1.02-1.19) and DM (aHR 1.13, 95%CI 1.03-1.25). There was also an increased risk for DL for the highest SVI tertile for the housing & transportation theme (aHR 1.61, 95%CI 1.10-2.37). Accumulation of de novo risk factors after HCT was associated with an incremental 5y incidence of CVD (None: 6.1%, 95% CI 3.4%-9.9%; 1 risk factor: 15.7%, 95% CI 7.1%-27.3%; >2 risk factors: 31.6%, 95%CI 12.8%-52.4%; p<0.001). In the adjusted multivariable model, survivors with >2 risk factors had 7.0-fold (aHR 6.99, 95%CI 2.86-17.05) risk of CVD compared to those without (ref). Conclusion: Among allogeneic HCT recipients, higher SVI was associated with increased risk of HTN, DM, and DL after HCT, which in turn were associated with incrementally higher 5y incidence of CVD. These findings underscore the importance of SDOH on clinically important outcomes after allogeneic HCT, and may ultimately inform tailored approaches for risk-based screening and resource allocation in long-term survivors. Citation Format: Osariemen V Ogiamien, Sitong Chen, Lizel Atencio, Alysia Bosworth, Meagan Echevarria, Caitlyn Estrada, Mareen Kassabian, Lanie Lindenfeld, F. Lennie Wong, Saro H Armenian, Rusha Bhandari. Social vulnerability is an important predictor of cardiovascular disease risk after allogeneic hematopoietic cell transplantation [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C044.