OBJECTIVES: With approvals of abiraterone acetate (AA) and enzalutamide (ENZA) in the past 2 years, the treatment landscape has shifted dramatically for metastatic castration-resistant prostate cancer (mCRPC) patients who failed docetaxel-based chemotherapy. There is increasing interest in the relative cost-effectiveness of these therapies. The objective of this study was to assess the cost-effectiveness of AA versus ENZA among individuals with mCRPC post chemotherapy from a payer perspective. METHODS: A survival-based Markov cohort model consisting of 3 health states, progression-free, progressed, and dead, was developed to project over 10 year period. Progression between states was determined by overall survival (OS) and radiographic progression free survival (rPFS).  An indirect treatment comparison was conducted to determine the relative efficacy of AA and ENZA (data reported separately).  Utilities were mapped from FACT-P to EQ-5D based on a review of the literature. Drug acquisition costs in the US were used since ENZA was approved only in the US at the time of analysis. Costs of scheduled and unscheduled follow-up visits were obtained from the Centers for Medicare Services Drug Payment Table and Physician Fee Schedule and represented in 2013 US dollars. Average wholesale prices for a 30-day supply of AA and ENZA were $7,674 and $8,940, respectively. One-way sensitivity analyses were performed against all probability, utility, and cost values incorporated into this cost-effectiveness model. RESULTS: In this analysis, AA provides substantial saving with $13,322 per patient versus ENZA. The main drivers of the model are drug costs, health utility values, and efficacy (OS and rPFS).  The robustness of the results was supported by sensitivity analyses. CONCLUSIONS: Given similar OS benefits, AA is cost saving compared with ENZA for the treatment of patients with mCPRC post-docetaxel based on US data.