Aims and background: Preclinical and clinical studies have suggested that aspirin (ASA) may exhibit antineoplastic activity. Particularly in prostate cancer, several reports have suggested that ASA plays a role in improved outcomes. Therefore, we studied the role of ASA in a uniquely African American population, which is known to harbor more aggressive and biologically different disease compared to the general population. Methods: We identified 289 African American men with prostate cancer who were treated with definitive radiation therapy to a dose of >= 7560 cGy. The median follow-up was 76 months. Kaplan-Meier analysis was used to analyze biochemical failure-free survival (bFFS), distant progression-free survival (DMPFS), and prostate cancer-specific survival (PCSS). Multivariate Cox regression was used to analyze the impact of covariates on all endpoints. Results: There were 147 men who were ASA+ and 142 who were ASA-. The 7-year bFFS was 80.9% for ASA+ men and 70.3% for ASA-men (p = 0.03). On multivariate analysis, ASA use was associated with a significant reduction in biochemical recurrences (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.34-0.93, p = 0.03). The 7-year DMPFS was 98.4% for ASA+ and 91.8% for ASA-men (p = 0.04). On multivariate analysis, ASA use was associated with a decreased risk of distant metastases (HR 0.23, 95% CI 0.06-0.91, p = 0.04). The 7-year PCSS was 99.3% for ASA+ and 96.9% for ASA-men (p = 0.07). Conclusions: In this study, ASA use was associated with improved biochemical outcomes and reduced distant metastases. This indicates that ASA appears to play an important antineoplastic role in African American men.