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Background: US Black men are on average diagnosed with more aggressive prostate cancer (PCa) and have higher mortality than White men. Studies in predominantly White populations show that PCa patients with pre-existing cardiovascular disease (CVD), metabolic syndrome (MetS), or prior CVD events face increased risk for further CVD and cardiotoxicity during/after androgen deprivation therapy (ADT). However, racial disparities in this context are underexplored. This study evaluates the impact of race, ADT use, and CVD on overall survival (OS) following radiation therapy (RT) for PCa, assessing disparities by stage and demographics. Methods: We conducted a retrospective review of a single institution prostate cancer database to identify patients with PCa who received IMRT or brachytherapy RT as their initial treatment between 2003 and 2023. Within each AJCC stage (I,II,III or IV), we compared OS curves by ADT use (any vs. none) and race, and by CVD (present vs. absent), and race using log-rank tests. Cox proportional hazards models were used to assess interactions and additionally adjust for age and substage (e.g. IIA vs IIB). Age was modeled as time-varying in stage II due to assumption violations. Descriptive statistics and chi-square tests compared baseline characteristics and CVD by race and ADT use. Results: Of 4,247 eligible patients (Black and White), 17% were Black, and 32% received ADT. Black patients were younger at diagnosis (mean 63.4 vs. 67.7 years, p<0.0001) and at more advance stage at diagnosis (Trend p=0.02). CVD affected 49% of patients, with no racial difference (p=0.48). ADT use increased by stage (5% to 85%), with no racial differences within stages (p>0.1). Median follow-up from end of RT to death or last follow-up was 85.4 months (IQR=43.5-139.8), with no difference by race (p=0.63). Among ADT patients, CVD was significantly associated with reduced OS in stage II (p = 0.02) and marginally in stage IV (p = 0.08). Age consistently predicted higher mortality across stages. CVD linked to increased mortality in stage I (HR 1.36, 95% CI 1.09–1.70, p=0.006), but not in later stages. Race was not independently associated with mortality. However, one significant interaction was found: In stage III only, ADT’s effect on survival differed by race. Among Black men, all deaths occurred in the ADT group (24/84) vs. none in the no-ADT group (0/9), HR was undefined; in contrast, among White men, OS was not associated with ADT, HR was 1.09 (95% CI 0.64–1.85). Conclusions: In this large, diverse cohort, CVD was common and linked to worse survival in early-stage PCa, especially in stage II ADT patients. Race did not independently predict mortality. ADT’s impact on survival did not differ significantly by race except in stage III, but interpretation was limited. CVD assessment in early stage PCa and larger studies to clarify ADT’s role in racial disparities in survival is needed.