Purpose: To assess diagnostic performance and reliability of Prostate-specific Membrane Antigen Reporting and Data System (PSMA-RADS) version 1.0 in evaluating prostate cancer (PCa) and compare it with the updated version (version 2.0). Materials and Methods: This prospective, multicenter study was conducted between June 2022 and August 2024. Participants with PCa underwent gallium 68 (68Ga) PSMA-11 PET/CT imaging and were divided into three groups: new diagnoses, biochemical recurrence (BCR), and follow-up. Three nuclear medicine radiologists independently interpreted the images using PSMA-RADS version 1.0, followed by a retrospective assessment using PSMA-RADS version 2.0. Diagnostic performance was calculated using linear mixed-model analysis. Histopathology and follow-up data served as reference standards. Interrater agreement was evaluated using the intraclass correlation coefficient (ICC). Results: The study included 443 male participants (mean age, 68.6 years ± 8.1 [SD]) divided into new diagnoses (n = 164), BCR (n = 108), and follow-up (n = 171) groups. Compared with PSMA-RADS version 1.0, version 2.0 improved diagnostic accuracy in new diagnoses (95.9% vs 97.4%, P = .02), BCR (92.6% vs 95.7%, P = .004), and follow-up (88.7% vs 94.7%, P < .001). Sensitivity substantially improved in follow-up cases (87.7% vs 95.7%, P < .001). Interrater agreement was comparable between two versions, with lowest reliability in soft tissue evaluation (ICC = 0.36–0.50). Introduction of the PSMA- RADS 5T category to version 2.0 enhanced the characterization of treated metastases, improving correlation with prostate-specific antigen dynamics (rs = 0.74 vs 0.61, P < .001) and the discrimination of treatment response (88.7% vs 82.3%, P = .02). Conclusion: Both PSMA-RADS versions 1.0 and 2.0 were highly accurate and reliable for PCa imaging, with version 2.0 offering significant improvements, particularly in challenging follow-up and BCR cases.