Objective To investigate the accuracy of prostate imaging and reporting data system (PI-RADS) score in diagnosing prostate cancer (PCa) with different prostate-specific antigen (PSA) levels. Methods Patients who underwent multiparametric magnetic resonance imaging scanning with biopsy of the prostate to obtain pathological confirmation in The First Affiliated Hospital of Naval Medical University (Second Military Medical University) between Jan. 2017 and Jun. 2023 were enrolled, and serum total PSA (t-PSA), free PSA (f-PSA), the ratio of free PSA to total PSA (f/t PSA) and PI-RADS scores were summarized in all patients. The accuracy of PI-RADS score in diagnosing PCa was analyzed at different PSA levels using pathology of the prostate biopsy as the gold standard. Results A total of 2 526 patients were enrolled and categorized into 7 groups according to the PSA level: 0-4 ng/mL, ＞4-10 ng/mL (f/t PSA≥0.16), ＞4-10 ng/mL (f/t PSA＜ 0.16), ＞10-20 ng/mL, ＞20-50 ng/mL, ＞50-100 ng/mL, and ＞100 ng/mL. In all patients, the sensitivity of PI-RADS≥3 in diagnosing PCa was 90.0%, which was superior to PI-RADS≥4 (sensitivity: 76.3%). Among the patients with PSA≤4 ng/mL, the accuracy of PI-RADS≥4 in diagnosing PCa was higher than that of PI-RADS≥3 (87.7% vs 64.0%). With the increase of PSA levels, the diagnostic accuracies of PI-RADS≥4 and PI-RADS≥3 were gradually increased and tended to be the same. When PSA was ＞50-100 ng/mL, the diagnostic accuracies of PI-RADS≥4 and ≥3 were 90.7% and 92.0%, respectively. Conclusion At higher PSA levels, the accuracies of PI-RADS scores in diagnosing PCa are higher, which can reduce unnecessary puncture of patients.