OBJECTIVES: There is no consensus regarding the optimal treatment for localized prostate cancer. This study aimed to examine the comparative effectiveness of monotherapy of either primary androgen deprivation therapy (PADT) or radical prostatectomy (RP) in terms of overall survival rate. METHODS: Male patients with localized prostate cancer were identified in the Veterans Affairs Veterans Integrated Service Network 16 data warehouse (January, 2003-June, 2006), with one year baseline and at least 3-year follow-up (till 06/2009). Eligible patients (18-75 years old) had no other cancer history and used PADT or monotherapy of RP within 6 months after the first diagnosis of prostate cancer. The overall survival from initiation of index treatment was analyzed using Kaplan-Meier method and Cox proportional hazard regression, adjusted for age, race, marital status, insurance type, cancer stage, Charlson comorbidity index, alcohol and tobacco use. RESULTS: The age was 66.2(6.07) [Mean(SD)] years in 211 PADT patients, 59.9(6.15) in 215 RP patients.  During the follow-up of 4.2(0.95) years, the cumulative incidence of death was 29 (13.74%) among PADT patients and 6 (2.79%) among RP patients (p<0.001). The overall 3-year survival rate was 89.57% in PADT and 98.60% in RP (p<0.001). Patients who received PADT had almost 4 times as high mortality risk as those using RP (HR =3.820, 95% CI=1.483 to 9.845, p=0.006). CONCLUSIONS: Overall survival rate following RP among localized prostate cancer patients was significantly higher than that after PADT, controlling for other covariates.  More research among a larger population with longer follow-up are warranted to confirm this finding.