Background: The assessment of comorbid cardiovascular disease can predict health outcomes and may risk-stratify patients for adverse events and death. Current methods used to estimate patient risk, such as the Charlson Comorbidity Index (CCI), are based on International Classification of Diseases (ICD) codes, which are a poor indicator of severity and complexity of comorbid disease. Alternatively, the number of cardiovascular drugs could be an efficient tool for estimating patient risk. In this study, we examined the relationship between cardiovascular medications and survival in patients being treated for metastatic hormone-sensitive prostate cancer (mHSPC). Methods: A nationwide retrospective observational study of US Veterans with de novo mHSPC in the Veterans Health Administration between 2011-2021 with at least 1 prescription medicine of any class. We determined the number of cardiovascular drugs from Anatomic Therapeutic Chemical (ATC) drug class C prescribed in the year prior up to 14 days before initiation of treatment. Multivariable logistic regression and Cox proportional hazard modeling was used to assess the association between number of drugs with overall survival (OS) while accounting for important covariates including age, body-mass index (BMI), prostate specific antigen (PSA), CCI, race, and weight change. Results: Among 7,875 veterans, a median (IQR) of 2 (1-4) unique cardiovascular medications were filled in the year prior to treatment. The mean age was 74.3 years (SD 10.0) with a median CCI of 3 (3-6). Age was associated with increased number of cardiac medicines with a mean of 1.6 drugs in <60 years, 2.2 drugs in 60-69, 2.5 drugs in 70-80, and 2.5 drugs in 80+ years (p<0.001). Increased number of medications was associated with decreased OS using the Kaplan-Meier method (p<0.001, see table). After adjusting for age, race, BMI, weight change, PSA, and CCI, the number of medications was independently associated with increased mortality with an adjusted hazard ratio (aHR) of 1.05 (1.03-1.06) for each additional cardiac drug. Increased mortality was observed in patients treated with 2 or more cardiac drugs (see table). Conclusions: The number of cardiovascular medications is associated with decreased survival in veterans undergoing treatment for mHSPC, even after accounting for important covariates including age, BMI, PSA, and CCI. The assessment of cardiovascular medications may provide a simple and reliable tool to estimate comorbid disease and survival in patients with cancer.