OBJECTIVES: Abiraterone and enzalutamide are two new treatment options for patients with mCRPC after docetaxel‑based chemotherapy. This study aims to understand the relative clinical and economic value of these therapies.  METHODS: Two pivotal clinical trials were conducted to evaluate abiraterone and enzalutamide in post-docetaxel treatment of mCRPC: Study COU-AA-301 for abiraterone and the AFFIRM trial for enzalutamide.  The PICO (population, intervention, comparison, and outcomes) construct was employed to assess the comparability of the trials, followed by an indirect treatment comparison (ITC) using the Bucher method and a mix treatment comparison using Bayesian statistics. An economic evaluation was performed based on the ITC results.    RESULTS: Several key differences were identified between the COU-AA-301 and AFFIRM trials.  First, the studies used different comparators. Abiraterone plus prednisone was compared with prednisone alone, while enzalutamide was compared with placebo.  Second, the endpoints rPFS, PSA progression, and PSA response were defined differently between trials, and thus were not included in the analysis. To address the difference in comparators, the ITC was performed using data from COU-AA-301 and subjects receiving corticosteroids concurrently in the AFFIRM trial. OS was significantly improved with both abiraterone and enzalutamide (3.9 and 3.2 months respectively). The ITC results were HR = 0.949 (95% CI: 0.712-1.26) for abiraterone versus enzalutamide using the Bucher method, and HR = 0.948 (95% CI: 0.711-1.26) using the Bayesian method. Using the US price for abiraterone and enzalutamide (approved in the US only), and assuming 25% of patients received therapy following docetaxel, cost savings from using abiraterone would be >$10K/patient/year or $49.0M/year nationally. CONCLUSIONS:  Differences in study design should be addressed when conducting an ITC.  The evidence from this ITC shows that abiraterone and enzalutamide have similar efficacy in OS in mCRPC post chemotherapy. However, abiraterone is cost saving compared to enzalutamide in this analysis.