OBJECTIVES: The treatment landscape of metastatic castration resistant prostate cancer (mCRPC) has changed with the introduction of novel agents. As little is known about their cost-effectiveness,  this study investigates the cost-effectiveness of radium-223 versus cabazitaxel, abiraterone and enzalutamide in Dutch mCRPC patients previously treated with docetaxel. METHODS: A cost-effectiveness analysis was conducted utilizing efficacy, symptomatic skeletal event (SSE) and safety data obtained from indirect treatment comparisons. As SSE data are unavailable for cabazitaxel, we conservatively assumed these to be identical to radium-223. A Markov model combined these clinical inputs with Dutch-specific resource use and costs for mCRPC treatment. Total quality-adjusted-life-years (QALYs) and costs were calculated over a 5-year horizon. Analyses were performed from a societal perspective. RESULTS: Radium-223 is associated with €4,535 and €5,905 lower lifetime costs and a difference of -0.004 and 0.02 QALYs compared to cabazitaxel and abiraterone, respectively. Sensitivity analyses reveal a 59% (78%) chance of radium-223 being cost-effective compared to cabazitaxel (abiraterone) at a €80,000 willingness to pay (WTP) threshold, the informal Dutch threshold. Compared to enzalutamide, radium-223 is associated with a slightly lower QALY gain (-0.06) and €7,255 lower lifetime costs, resulting in only a 19% chance of enzalutamide being cost-effective compared to radium-223 at a €80,000 WTP threshold. Sensitivity analyses reveal a 74%, 80% and 78% chance of radium-223 being cost-saving compared to cabazitaxel, abiraterone and enzalutamide, respectively.Radium-223’s lower lifetime costs compared to abiraterone and enzalutamide are driven by less drug costs and prevention of expensive SSE’s. Compared to cabazitaxel, radium-223’s savings are driven by fewer costs of the drug, administration and adverse event treatment. CONCLUSIONS: Our model shows that while QALY gains are in the same ballpark (a maximum absolute difference of 0.06 QALY), radium-223 is a cost-saving treatment compared to cabazitaxel, abiraterone and enzalutamide in Dutch mCRPC patients previously treated with docetaxel.