Background: Clinical trials provide high-level evidence and test novel therapies that have significantly improved cancer outcomes. However, disparities in clinical trial participation and cancer mortality persist across race/ethnicity and vulnerable populations, notably in patients with prostate cancer (PCa). Adverse social determinants of health (SDOH) and systemic barriers may underlie these disparities. Identifying and overcoming these barriers may improve access to and representation in clinical trials, thereby promoting equitable advancement and applicability of science. For these reasons, we evaluate the association between clinical trial availability, cancer mortality, and population-level SDOH in PCa. Methods: Using custom data linkage from ClinicalTrials.gov, Surveillance Epidemiology and End Results (SEER) Registry, and the Centers for Disease Control and Prevention Social Vulnerability Index (SVI), we performed a cross-sectional analysis of county-level PCa clinical trial data, cancer incidence and mortality rates, and population-level SDOH. We included Phase 2 and Phase 3 interventional PCa clinical trials with start dates from 2007 to 2022. The total number of clinical trials over the study period was calculated per county and population-adjusted for 100,000 residents. Counties were stratified into quintiles based on SVI (i.e., least vulnerable to most vulnerable). Population-adjusted clinical trial availability, cancer incidence, and cancer mortality were compared across SVI quintiles. Multivariable logistic and linear regression analyses were performed to evaluate the association between SVI and clinical trial availability and cancer mortality, respectively. Results: The mean number of PCa trials per 100,000 residents was 25.6, with the most vulnerable counties having fewer clinical trials compared to the least vulnerable counties (mean 18.1 vs. 50.0, p<0.05). Further, the most vulnerable counties had a lower PCa incidence rate per 100,000 residents (mean 393.8 vs. 411.7, p<0.05), but a higher PCa mortality rate per 100,000 residents (mean 85.7 vs. 72.0, p<0.05). On multivariable regression analysis, the most vulnerable counties were associated with significantly decreased odds of having any PCa clinical trial (OR 0.3, 95% CI 0.2 – 0.4) and significantly increased PCa mortality (10.8, 95% CI 7.4 – 14.3), while the presence of any PCa clinical trial was associated with significantly decreased PCa mortality (-6.9, 95% CI -9.1 – -4.7). Conclusions: The most vulnerable counties were far less likely to have any PCa clinical trials despite having a significantly higher PCa mortality rate. The presence of a PCa clinical trial was associated with a reduction in PCa mortality. These vulnerable counties represent scientifically underserved populations that may benefit from equity-driven clinical trial enrollment and cancer care infrastructure expansion.