OBJECTIVES:: To calculate costs per monthly median overall survival (OS) in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate plus prednisone (AA+P) or enzalutamide. METHODS:: Median treatment duration and median OS data from published Phase 3 clinical trials and prescribing information were used to calculate costs per monthly median OS based on ex-factory price (EFP) for patients with mCRPC treated with AA+P or enzalutamide. Sensitivity analyses were performed to understand how variations in treatment duration and treatment-related monitoring recommendations influenced cost per median OS. Cost-effectiveness estimates of other Phase 3 trial outcomes were also explored: Cost per month of chemotherapy avoided and per median radiographic progression-free survival (rPFS). RESULTS:: The results demonstrated that AA+P has a lower cost per monthly median OS than enzalutamide ($846.00 vs. 1,573.00; 46% reduction), based on the following assumptions: exchange rate USD 1 = COP 2967, median treatment duration of 14 months for AA+P and 18 months for enzalutamide, median OS of 34.7 months for AA+P and 35.3 months for enzalutamide, and EFP per 30-day supply of $2,096.57 for AA+P versus $3,084.11 for enzalutamide. Sensitivity analyses showed that accounting for recommended treatment-related monitoring costs or assuming identical treatment durations for AA+P and enzalutamide (18 months) resulted in costs per median OS month 31% to 44% lower for AA+P than for enzalutamide. Costs per month of chemotherapy avoided were $1,165.00 for AA+P and $1,983.00 for enzalutamide, while costs per month to achieve median rPFS were $1,779.00 for AA+P and $2,776.00 for enzalutamide. CONCLUSIONS:: Costs per monthly median OS, along with costs of other Phase 3 trial outcomes, were lower for AA+P than for enzalutamide. The findings were robust to sensitivity analyses. These results have important implications for population health decision makers evaluating the relative value of therapies for mCRPC patients.