•In TZ, PI-RADS v2.1 had better inter-reader reproducibility than did PI-RADS v2.•PI-RADS v2.1 may contribute to increased diagnostic performance of TZ tumor.•PI-RADS v2.1 still showed a high false positive rate for TZ tumor detection. To compare the diagnostic performance of PI-RADS v2 and v2.1 for detecting transition zone prostate cancer (TZPC) on multiparametric prostate MRI (mpMRI). Fifty-eight patients with elevated PSA levels underwent mpMRI at 3 T including T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), and subsequent MRI–transrectal ultrasonography fusion-guided prostate-targeted biopsy (MRGB). The standard of reference was MRGB-derived histopathology. Two readers independently assessed each TZ lesion, assigning a score of 1–5 for T2WI, a score of 1–5 for DWI, and the overall PI-RADS assessment category according to PI-RADS v2 and v2.1. The diagnostic performance of the two methods was compared in terms of inter-reader agreement, diagnostic sensitivity, diagnostic specificity, and area under the ROC curve (AUC). Of the 58 patients, 26 were diagnosed with PC (GS = 3 + 3, n = 9; GS = 3 + 4, n = 9; GS = 3 + 5, n = 1; GS = 4 + 3, n = 4; GS = 4 + 4, n = 3) and 32 with benign lesions. Regarding inter-reader agreement of overall PI-RADS assessment category, the kappa value was 0.580 for v2 and 0.645 for v2.1. For both readers, there was no difference in diagnostic sensitivity between the versions (p ≥ 0.500). For reader 1, the diagnostic specificity was higher for v2.1 (p = 0.002), and was similar for reader 2 (p = 1.000). For both readers, AUC tended to be higher for v2.1 than for v2, but the difference was not significant (0.786 vs. 0.847 for reader 1, p = 0.052; and 0.808 vs. 0.858 for reader 2, p = 0.197). These results suggest that compared with PI-RADS v2, PI-RADS v2.1 could be preferable for evaluating TZ lesions.