BackgroundMultiparametric MRI (mp-MRI) combined with machine-aided approaches have shown high accuracy and sensitivity in prostate cancer (PCa) diagnosis. However, radiomics-based analysis has not been thoroughly compared with Prostate Imaging and Reporting and Data System version 2 (PI-RADS v2) scores. PurposeTo develop and validate a radiomics-based model for differentiating PCa and assessing its aggressiveness compared with PI-RADS v2 scores. Study TypeRetrospective. PopulationIn all, 182 patients with biopsy-proven PCa and 199 patients with a biopsy-proven absence of cancer were enrolled in our study. Field Strength/SequenceConventional and diffusion-weighted MR images (b values=0, 1000 sec/mm(2)) were acquired on a 3.0T MR scanner. AssessmentA total of 396 features and 385 features were extracted from apparent diffusion coefficient (ADC) images and T2WI, respectively. A predictive model was constructed for differentiating PCa from non-PCa and high-grade from low-grade PCa. The diagnostic performance of each radiomics-based model was compared with that of the PI-RADS v2 scores. Statistical TestsA radiomics-based predictive model was constructed by logistic regression analysis. 70% of the patients were assigned to the training group, and the remaining were assigned to the validation group. The diagnostic efficacy was analyzed with receiver operating characteristic (ROC) in both the training and validation groups. ResultsFor PCa versus non-PCa, the validation model had an area under the ROC curve (AUC) of 0.985, 0.982, and 0.999 with T2WI, ADC, and T2WI&ADC features, respectively. For low-grade versus high-grade PCa, the validation model had an AUC of 0.865, 0.888, and 0.93 with T2WI, ADC, and T2WI&ADC features, respectively. PI-RADS v2 had an AUC of 0.867 in differentiating PCa from non-PCa and an AUC of 0.763 in differentiating high-grade from low-grade PCa. Data ConclusionBoth the T2WI- and ADC-based radiomics models showed high diagnostic efficacy and outperformed the PI-RADS v2 scores in distinguishing cancerous vs. noncancerous prostate tissue and high-grade vs. low-grade PCa. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:875-884.