To assess the accuracy of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) in detecting clinically significant prostate cancer (csPCa) on multiparametric magnetic resonance imaging (mpMRI) using whole-mount sections after radical prostatectomy (RP) as reference standard.Forty-eight patients undergoing mpMRI before RP were prospectively enrolled. Two experienced radiologists independently scored and mapped imaging findings according to PI-RADS v2. One experienced uropathologist mapped cancers detected on whole-mount sections using the PI-RADS v2 sector scheme. Per-lesion and per-patient analyses were run. Primary outcomes were sensitivity and false discovery rate (FDR) in detecting csPCa using PI-RADS v2 score ≥3 and ≥4 as thresholds. Secondary outcome was inter-reader agreement.On the per-lesion analysis, sensitivity and FDR at the PI-RADS v2 threshold score ≥3 were 0.75 and 0.17 for Reader 1, and 0.67 and 0.13 for Reader 2, respectively. At the PI-RADS v2 threshold score ≥4, sensitivity was slightly lower, and FDR nearly halved for both readers. On the per-patient analysis, sensitivity for csPCa at the PI-RADS v2 threshold score ≥3 was 0.85 for Reader 1, and 0.78 for Reader 2. At the PI-RADS v2 threshold score ≥4, sensitivity was slightly lower for both readers. Inter-reader agreement was substantial (k 0.72 and 0.65 for PI-RADS v2 threshold score ≥3 and ≥4, respectively).In our prospective study with pathology after RP as standard of reference, PI-RADS v2 showed good sensitivity in detecting csPCa on mpMRI with substantial agreement between 2 experienced readers. Threshold score ≥4 had lower FDR.