OBJECTIVES: We compared patterns of mortality among men with prostate cancer at 2 Department of Veterans Affairs (VA) and 2 private-sector hospitals in the Chicago area. METHODS: Mortality rates for 864 cases diagnosed between 1986 and 1990 were estimated using Cox proportional hazards models that incorporated age; income; cancer stage, differentiation, and treatments; and baseline comorbidity. RESULTS: Race tended to associate with all-cause mortality irrespective of health care setting (Blacks vs Whites: hazard rate ratio [HRR] = 1.68 [95% confidence interval (CI) = 1.06, 2.67]; P <.001 in the private sector; HRR = 1.50 [95% CI = 0.94, 2.38]; P =.088 in the VA). However, comorbidity determined risk in the VA, whereas age and income predicted risk in the private sector. CONCLUSIONS: Determinants of all-cause mortality in men with prostate cancer vary according to health care setting.