Objective: The radiopharmaceuticals radium-223 and the pharmacy preparation 177 Lu-PSMA-I&T are reimbursed in the Netherlands for metastatic castration-resistant prostate cancer (mCRPC) treatment. Although shown to be life-prolonging in patients with mCRPC, the treatment procedures associated with these radiopharmaceuticals can be challenging for both patients and hospitals. This study investigates the costs of mCRPC treatment in Dutch hospitals for currently reimbursed radiopharmaceuticals with a demonstrated overall survival benefit. Methods: A cost model that calculated the direct medical per-patient costs of radium-223 and 177 Lu-PSMA-I&T was developed, following clinical trial regimens. The model considered six 4-weekly administrations (i.e. ALSYMPCA regimen) of radium-223. Regarding 177 Lu-PSMA-I&T, the model used both the VISION regimen (i.e. five 6-weekly administrations) and the SPLASH regimen (i.e. four 8-weekly administrations). Based on health insurance claims, we also estimated the coverage a hospital would receive for providing treatment. No fitting health insurance claim for 177 Lu-PSMA-I&T is currently available; therefore, we calculated a break-even value for a potential health insurance claim that would exactly counterbalance the per-patient costs and coverage. Results: Radium-223 administration is associated with per-patient costs of €30,905, and these costs are fully covered by the coverage a hospital receives. The per-patient costs of 177 Lu-PSMA-I&T range between €35,866 and €47,546 per administration period, depending on the regimen. Current healthcare insurance claims do not fully cover the costs of providing 177 Lu-PSMA-I&T: hospitals must pay €4,414–€4,922 for each patient out of their own budget. The break-even value for the potential insurance claim covering 177 Lu-PSMA-I&T administration with a VISION (SPLASH) regimen is €1,073 (€1,215). Conclusion: This study shows that, without consideration of the treatment effect, radium-223 treatment for mCRPC leads ...