Background: Evidence concerning third-line life-prolonging drugs (LPDs) in the treat-ment of metastatic castration-resistant prostate cancer (mCRPC) patients is incomplete. Objective: To evaluate third-line LPD outcomes in a real-world cohort of mCRPC patients, identify variables associated with overall survival (OS), and establish a prog-nostic model. Design, setting, and participants: Patients with mCRPC who were progressive on second-line LPD before July 1, 2017 were retrospectively identified from the Dutch Castration-resistant Prostate Cancer Registry (CAPRI) and followed until December 31, 2017. Outcome measurements and statistical analysis: Association of potential risk factors with OS was tested by Cox proportional hazard models after multiple imputation of missing baseline characteristics. A predictive score was computed from the regression coefficient and used to classify patients into risk groups. Results and limitations: Of 1011 mCRPC patients progressive on second-line LPD, 602 (60%) received third-line LPD. Patients receiving third-line LPD had a more favorable prognostic profile at baseline and longer median OS than patients with best supportive