OBJECTIVES:  More recent advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been associated with higher costs. In the light of the current efforts to ensure affordable cancer treatment in Greece, the cost-effectiveness of newer drug treatments should be constantly monitored. The aim of this study was to assess the clinical outcomes and costs of mCRPC therapy in the real-life clinical setting in Greece. METHODS:  This observational retrospective cohort study was conducted on all the mCRPC patients treated over a 3 year period, at two major Oncology Hospitals in Athens, Greece. In total, data were collected from the medical files of 42 male mCRPC patients, mean age 73.1(SD 7.8) years. Primary outcome measures included direct monthly medical costs (medications, laboratory and diagnostic tests, hospitalizations) and clinical outcomes (% variation in PSA levels and number of days free of the disease) for each patient. Incremental cost-effectiveness ratios (ICER) were calculated as a secondary outcome measure. RESULTS:  Monthly (mean±SD) single-drug administration of docetaxel was found to be the least costly (€859±258) of all the chemotherapeutic (single or sequential) protocols (€3121±330- €6262±1266), but more costly in terms of supportive care than the other newer single-drug treatments, except cabazitaxel (p<0.05). On the other hand, clinical outcomes of therapy, based on the mean ratio of days free of disease/days of chemotherapy, suggested that abiraterone (0.87±0.35 days) was more effective than docetaxel (0.71±0.31 days) (p=0.029). Also based on the ICERS, single-drug abiraterone therapy was found to be more effective/more costly than docetaxel alone and more effective/less costly than sequential docetaxel plus abiraterone. Due to the small patient sample, data relating to the costs and clinical outcomes of cabazitaxel and enzalutamide therapies were inconclusive. CONCLUSIONS: The results of this study provide an insight into the cost-effectiveness of conventional and newer therapies for mCRPC in Greece.