Purpose: Progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC) trials has been inconsistently defined and poorly associated with overall survival (OS). A reproducible quantitative definition of radiographic PFS (rPFS) was tested for association with a coprimary end point of OS in a randomized trial of abiraterone in patients with mCRPC. Patients and Methods: rPFS was defined as ��� two new lesions on an 8-week bone scan plus two additional lesions on a confirmatory scan, ��� two new confirmed lesions on any scan ��� 12 weeks after random assignment, and/or progression in nodes or viscera on cross-sectional imaging, or death. rPFS was assessed by independent review at 15% of deaths and by investigator review at 15% and 40% of deaths. rPFS and OS association was evaluated by Spearman's correlation. Results: A total of 1,088 patients were randomly assigned to abiraterone plus prednisone or prednisone alone. At first interim analysis, the hazard ratio (HR) by independent review was 0.43 (95% CI, 0.35 to 0.52; P <.001; abiraterone plus prednisone: median rPFS, not estimable; prednisone: median rPFS, 8.3 months). Similar HRs were obtained by investigator review at the first two interim analyses (HR, 0.49; 95% CI, 0.41 to 0.60; P <.001 and HR, 0.53; 95% CI, 0.45 to 0.62; P <.001, respectively), validating the imaging data assay used. Spearman's correlation coefficient between rPFS and OS was 0.72. Conclusion: rPFS was highly consistent and highly associated with OS, providing initial prospective evidence on further developing rPFS as an intermediate end point in mCRPC trials.