Objective To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). Methods This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. Results For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 95% CI 0.923–0.976) than PI-RADS (Az: 0.878 0.834–0.914, p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 0.945–0.988 vs. 0.940 0.905–0.965, p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 0.960–0.995) and PCa versus TZ (Az: 0.968 0.940–0.985). Conclusion Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa. Key Points • Machine - based analysis of MR radiomics outperformed in TZ cancer against PI - RADS . • Adding MR radiomics significantly improved the performance of PI - RADS . • DKI - derived Dapp and Kapp were two strong markers for the diagnosis of PCa .