Objective: The aim of this study is to evaluate the utility of quantitative apparent diffusion coefficient (ADC) measurements and normalized ADC ratios in multiparametric MRI for the diagnosis of clinically significant peripheral zone (PZ) prostate cancer particularly among equivocally suspicious prostate lesions. Methods: A retrospective analysis of 95 patients with PZ lesions by PI-RADSv2 criteria, and who underwent subsequent MRI-US fusion biopsy, was approved by an institutional review board. Two radiologists independently measured ADC values in regions of interest (ROIs) of PZ lesions and calculated normalized ADC ratio based on ROIs in the bladder lumen. Diagnostic performance was evaluated using ROC. Inter observer variability was assessed using intraclass correlation coefficient (ICC). Results: Mean ADC and normalized ADC ratios for clinically significant and non-clinically significant lesions were 0.763 × 10-3 mm2 s-1, 29.8%; and 1.135 × 10-3 mm2 s-1, 47.2% (p < 0.001), respectively. Area under the ROC curve (AUC) was 0.880 [95% CI (0.816-0.944) and 0.885 (95% CI (0.814-0.955)] for ADC and ADC ratio, respectively. Optimal AUC threshold for ADC was 0.843 × 10-3 mm2 s-1 (Sn 70.5%, Sp 88.2%) and for normalized ADC was 33.1% (Sn 75.0%, Sp 95.7%). intraclass correlation coefficient was high at 0.889. Conclusion: Quantitative ADC measurement in PZ prostate lesions demonstrates excellent diagnostic performance in differentiating clinically significant from non-clinically significant prostate cancer with high inter observer correlation. Advances In knowledge: Quantitative ADC is presented as an additional method to evaluate lesions in mpMRI of the prostate. This technique may be incorporated in new and existing methods to improve detection and discrimination of clinically significant prostate cancer.