Background This study aimed to address long-term survival in a large population-based cohort of men with prostate cancer receiving radical prostatectomy compared to other treatments. Methods We studied 5,845 patients diagnosed with local/regional stage prostate cancer at age 65–74 in 1992 with comorbidity score <2, who were defined as potential candidates for radical prostatectomy and identified from the SEER (Surveillance, Epidemiology and End Results)-Medicare cohort with median follow-up of 11 years. Results Of 5,845 patients, 10-year all-cause survival rates were the highest for patients receiving radical prostatectomy (81.0%; 95% CI: 79.4–82.4%), followed by radical prostatectomy in combination with radiotherapy (67.6%; 62.0–72.5%), radiotherapy (60.5%; 58.3–62.6%), and were the lowest for watchful-waiting (50.7%; 47.5–53.8%). A similar pattern was found for 10-year prostate cancer-specific survivals by treatments. After adjusting for age, ethnicity, region, Gleason Score, comorbidity, median annual household income, hormone therapy and chemotherapy, the hazard ratio of all-cause mortality was 0.31 (95% CI: 0.25–0.37) for radical prostatectomy and 0.38 (95% CI: 0.28–0.52) for radical prostatectomy plus radiation therapy compared to those with watchful-waiting. Conclusions There was a significant long-term survival benefit in men receiving radical prostatectomy compared to those receiving watchful-waiting or radiotherapy. J. Surg. Oncol. 2008;97:583–591. © 2008 Wiley-Liss, Inc.