Objective: To evaluate the cost-effectiveness of radical prostatectomy (RP), external beam radiotherapy (EBRT) monotherapy, and EBRT+brachytherapy for men with very high-risk prostate cancer (VHRPC). Methods: Using a decision tree with embedded Markov process models, a cost-utility analysis was performed comparing the three treatment strategies for hypothetical cohorts of men with VHRPC. The base case time horizon was ten years; consistent with the maximum follow-up reported in the literature. The model parameters for distant metastases and mortality were derived from a multi-institutional study utilizing patient-level data. Costs were from a societal standpoint and health state utilities were obtained via standard gamble techniques. Incremental cost-effectiveness ratios were calculated per quality-adjusted life year using a 3% discount rate. Sensitivity analyses (SA) addressed uncertainty in key variables. Findings: EBRT+brachytherapy was both cost-saving and more effective than both EBRT monotherapy and RP, strongly dominating both alternative treatment strategies. These results remained robust to extensive SA.