OBJECTIVES: Whether the addition of radiation therapy (RT) improves overall cost effectiveness in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is still unclear. Our objective was to conduct cost-effectiveness analysis of adding radiation therapy to androgen deprivation therapies in men with locally advanced prostate cancer in the U.S.A. METHODS: A decision analysis model was designed to compare adding RT to ADT over a 10 year time horizon with the third party payer’s perspective. Probabilities of treatment success, utilization of salvage treatments, and rates of adverse events were taken from published results of SPCG-7/SFUO-3 trial and NCIC CTG PR.3/MRC UK PR07 trial. Cost inputs were based on 2010 Medicare reimbursement rates and reported in 2013 US dollars. Primary outcome measure was incremental cost per biochemical success (i.e. serum PSA level <0.4 ng/ml). 50,000 U.S. dollars were considered willingness to pay threshold.  A series of one-way sensitivity analyses and Monte Carlo simulation was performed by testing variations in the range of the 95% confidence interval. RESULTS: ART results in a higher biochemical success rate than hormonal therapy with a probability of 0.30 versus 0.21. The mean incremental effect was 0.6 over a 10-year period. Total cost of ART was $25,783 compared with costs in the ADT group of $13,427 per year, the mean incremental cost for ART versus ADT was $8,277 over 10 year period. The mean incremental cost effectiveness ratio was $13758 over 10 year period. Cost-effectiveness acceptability curve analysis resulted in >90% probability that ART with hormonal therapy is cost-effective strategy. CONCLUSIONS: Study suggests that adding RT to ADT is cost effective strategy compared to ADT alone based upon the decision analysis model for appropriate men with locally advanced prostate cancer. The study limitations and treatment dosage should be considered before applying the results of the study.