OBJECTIVES:   To compare the costs and outcomes of enzalutamide vs. abiraterone for the treatment of docetaxel refractory metastatic castrate resistant prostate cancer (mCRPC) from a limited societal perspective using a lifetime horizon. METHODS: We developed a Markov model with 3 health states: pre-progression, post-progression, and death with 1 month transitions. Transition probabilities for all health states were derived from the pivotal phase 3 clinical trials: AFFIRM (enzalutamide) and COU-AA-301 (abiraterone). A 3% discount was applied to all costs and outcomes. Costs included drug acquisition costs, laboratory tests associated with treatment, as well as costs for grade 3/4 side effects management. Outcomes were assessed in quality-adjusted life-years (QALYs). We conducted 16 univariate sensitivity analyses varying model inputs (overall survival, progression-free survival, utility, drug acquisition cost) for each respective drug independently by 20%. RESULTS: In the base case analysis, we found that the costs for enzalutamide were higher than that of abiraterone, primarily due to higher acquisition costs ($84465, $74119 respectively). Enzalutamide was also associated with greater life years gained than abiraterone (1.39, 1.30 respectively) as well as QALYs gained (1.24, 1.05 respectively). The ICER was $55070/QALY. Sensitivity analyses indicated that the ICER varied widely; using commonly accepted thresholds of $50000/QALY and $100000/QALY, we found that out of the 16 sensitivity analyses conducted, 4 fell below the $50000/QALY threshold and 7 fell below the $100000/QALY threshold. CONCLUSIONS: The treatment landscape of mCRPC has shifted dramatically in recent years. Where there previously had been few options for patients, the last 2 years have brought multiple new therapies for mCRPC. To our knowledge, this is the first study which compares the cost-effectiveness of enzalutamide to abiraterone. Our results suggest that there is considerable uncertainty regarding the cost-effectiveness of enzalutamide, but enzalutamide will likely play a significant role in the treatment of mCRPC.