To evaluate cause-specific mortality following radical prostatectomy (RP) in a population cohort of US men adjusting for competing risks.The Surveillance, Epidemiology and End Results (SEER) database was used to identify 120,392 men undergoing RP for clinically localized prostate cancer between 1988 and 2003. Cause-specific mortality data were extracted through 2006 and cumulative incidence was estimated using a competing risks approach.The stage distribution of the cancers was 32% local, 28% regional, 40% unknown, and 80% of tumors Gleason ≤ 7. Median follow-up was 7 years. The 15-year prostate cancer-specific mortality was 5.3% and the non-prostate cancer mortality was 30.6%. Stage, grade and race had minimal impact on non-prostate cancer mortality. At 15 years following surgery, mortality due to cardiovascular diseases was 11%, other cancers 9.1%, and other causes 10.5%. Among men ≥ 65 years, 15-year cancer-specific mortality was 6% and non-prostate cancer mortality was 40.8%.Following RP, death from cardiovascular diseases, other cancers, and other causes is far more common than death from prostate cancer. In men diagnosed with prostate cancer, significant efforts should be made to prevent, diagnose, and treat these diseases.