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BACKGROUND Following the recent publication of results from randomized trials that have demonstrated a survival benefit for the addition of docetaxel or abiraterone acetate to androgen deprivation therapy (ADT) in the treatment of metastatic prostate cancer, it is important to assess whether the benefits of treatment with these agents outweigh their costs. OBJECTIVE To perform a cost-effectiveness analysis of immediate docetaxel or abiraterone acetate treatment in addition to ADT in men with metastatic hormone-sensitive prostate cancer (PC). DESIGN, SETTING, AND PARTICIPANTS We developed a state-transition model to simulate the natural progression of metastatic PC. Model parameters were derived from the published literature and through calibration to observed epidemiological data. Following diagnosis, a hypothetical cohort of men with metastatic hormone-sensitive PC could be treated with docetaxel+ADT, abiraterone+ADT, or ADT alone. Once disease progresses to castration-resistant PC, treatment with one of the approved therapies in this setting was initiated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The outcomes measured were quality-adjusted life years (QALYs) and costs from a US private payer, health sector perspective. RESULTS AND LIMITATIONS Compared to treatment with ADT alone, docetaxel and abiraterone resulted in a discounted quality-adjusted survival gain of 3.6 and 22.0mo, respectively. Using standard cost-effectiveness metrics, treatment with docetaxel and ADT provides high value for money (ie, is cost effective) with an incremental cost-effectiveness ratio (ICER) of $34723, compared to an ICER of $295212 for abiraterone. The monthly cost of abiraterone would have to be less than $3114 for it to be cost effective. CONCLUSIONS Docetaxel+ADT is likely the most cost-effective treatment option for men with metastatic hormone-sensitive PC. Although potentially more effective than docetaxel, the costs of abiraterone would have to be considerably lower to match the cost effectiveness of docetaxel+ADT. PATIENT SUMMARY This study evaluated the balance of costs and benefits for treatment of metastatic hormone-sensitive prostate cancer with docetaxel plus androgen deprivation therapy (ADT), abiraterone plus ADT, or ADT alone. We found that treatment with docetaxel plus ADT likely represents the most cost-effective option in this setting.