Background There appears to be less agreement in the identification of cancers in the transition zone (TZ), which is not as reliable as those in peripheral zone when using the Prostate Imaging Reporting and Data System (PI‐RADS) version 2 (v2). In response to such shortcomings, the updated version 2.1 was introduced, which incorporated diffusion‐weighted imaging (DWI) into category 2 and clarified lexicons. Purpose To compare the diagnostic performance for the detection of clinically significant TZ prostate cancers (csPCa) and interreader agreement between PI‐RADS v2.1 and v2. Study Type Retrospective study. Population In all, 142 patients, 201 TZ lesions. Field Strength/Sequence 3.0T; T2‐weighted image and DWI. Assessment Lesions were scored by three independent readers using PI‐RADS v2 and v2.1. Statistical Tests The sensitivity and specificity at category ≥3 were compared between v2 and v2.1 using the generalized estimating equation model. Detection rates for csPCa of upgraded and downgraded lesions in the use of PI‐RADS v2.1 from v2 were assessed. Interreader agreement was assessed using κ statistics. Results PI‐RADS v2.1 showed a higher sensitivity and specificity (94.5% and 60.9%) than v2 (91.8% and 56.3%) for category ≥3 lesions in the detection of csPCa, although not significantly. Of eight upgraded lesions from category 2 to 3 (2 + 1) with an incorporated DWI, 50% (4/8) were csPCa. This was significantly higher than category 2 lesions (4.4%; P = 0.003). No csPCa was detected among the 22.8% (46/201) downgraded lesions. There was a moderate interreader agreement for scores ≥3 (κ = 0.565) in v2.1, which was slightly higher than that for v2 (κ = 0.534), although not significantly. Data Conclusion PI‐RADS v2.1 provides moderate and comparable interreader agreement at category ≥3 than v2 in the TZ lesions. Upgraded lesions from category 2 to 3 demonstrated a higher detection rate of csPCa than category 2 lesions in v2.1. Level of Evidence 4 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2020;52:577–586.