OBJECTIVES: Abiraterone acetate plus predniso(lo)ne (AA+P) and enzalutamide (ENZ) are novel anti-androgen therapies for the treatment of metastatic castration-resistant prostate cancer (mCRPC) that are approved in both the pre-chemotherapy and post-chemotherapy settings. The aim of this study is to estimate and compare the costs associated with two treatment sequences: AA+P followed by docetaxel (DOC) chemotherapy and then ENZ (‘AA+P-DOC-ENZ sequence’) versus ENZ followed by DOC chemotherapy and then AA+P  (‘ENZ-DOC-AA+P sequence’) in mCRPC patients with non-visceral metastases. METHODS:  A health economic model has been developed to estimate and compare the cost consequences of these two treatment sequences in the UK. Seven health states were considered in the model: pre chemotherapy treatment (AA+P or ENZ), active monitoring (before and after chemotherapy separately), DOC chemotherapy, post-chemotherapy treatment (AA+P or ENZ), best supportive care, and death. Clinical input data (e.g., duration of treatment, time to chemotherapy) for the model were derived from published pivotal trial results. Costs parameters were derived from available literature and the manufacturers’ published reimbursement submission dossiers. List prices of drugs were used. For each treatment sequence, the model estimated total costs and total costs per health state. RESULTS: The total costs were estimated to be £75,956 for the ‘AA+P-DOC-ENZ sequence’ and £80,591 for the ‘ENZ-DOC-AA+P sequence’ resulting in a total cost difference of £4,636. Pre-chemotherapy costs of AA+P and ENZ treatment were estimated to be £43,817 and £48,860, respectively (difference £5,043). With respect to the other health states, similar costs were estimated for the two sequences, e.g., post-chemotherapy costs of AA+P and ENZ treatment were predicted to be £9,481 and £8,974, respectively. CONCLUSIONS: The results of the health economic model suggest that the ‘AA+P-DOC-ENZ sequence’ yields lower total costs than the ‘ENZ – DOC- AA+P sequence’ and therefore starting treatment with AA+P may result in cost savings.