Background: African American (AA) men are known to develop more aggressive forms of prostate cancer at a younger age compared to their Non-Hispanic White (NHW) counterparts. However, few AA men were included in the major randomized trials assessing the efficacy of Prostate-Specific Antigen (PSA) screening. It is thus unknown whether PSA screening may be more beneficial in the AA population. Methods: We conducted a retrospective analysis of men diagnosed with prostate cancer in the United States (US) Veterans Affairs Health System (VA) using the VA Informatics and Computing Infrastructure. Inclusion criteria were AA or NHW men aged 55-69 diagnosed with intermediate or high-risk prostate cancer between 2004 and 2017. Patients were classified as never screened with PSA prior to diagnosis, screened at least once prior to diagnosis (some screening), or screened in 5 consecutive years prior to diagnosis (annual screening). A lead-time bias adjusted multivariate regression model was implemented to assess the effect of screening on prostate cancer specific mortality (PCSM), with covariates including age, comorbidities, BMI, smoking history, marital status and primary care utilization. Results: A total of 45,825 men met the inclusion criteria and were included in the analysis, including 14,294 (31.1%) AA men and 31,151 (68.9%) NHW men. When compared to no screening, any prior PSA screening was associated with improved PCSM for both AA (subdistribution hazard ratio (SHR) 0.64, p < 0.001) and NHW (SHR 0.62, p < 0.001) patients. Annual PSA screening (vs no or some screening) was associated with improved PCSM for AA men (SHR 0.68, p = 0.013) but not NHW men (SHR 0.90, p = 0.240). Other significant predictors of worse PCSM in both AA and NHW men included older age, earlier year of diagnosis, greater comorbidity burden, and cigarette smoking. Conclusions: In a diverse population of US veterans, at least one prior screening PSA was associated with improved PCSM in both AA and NHW patients. Annual PSA screening was associated with reduced PCSM in AA but not NHW men, suggesting that more intensive screening protocols may be beneficial for AA patients.