OBJECTIVE: To analyse serial changes in MRI-derived tumour measurements and apparent diffusion coefficient (ADC) values in prostate cancer (PCa) patients on active surveillance (AS) with and without histopathological disease progression. METHODS: This study included AS patients with biopsy-proven PCa with a minimum of two consecutive MR examinations and at least one repeat targeted biopsy. Tumour volumes, largest axial two-dimensional (2D) surface areas, and maximum diameters were measured on T2 weighted images (T2WI). ADC values were derived from the whole lesions, 2D areas, and small-volume regions of interest (ROIs) where tumours were most conspicuous. Areas under the ROC curve (AUCs) were calculated for combinations of T2WI and ADC parameters with optimal specificity and sensitivity. RESULTS: 60 patients (30 progressors and 30 non-progressors) were included. In progressors, T2WI-derived tumour volume, 2D surface area, and maximum tumour diameter had a median increase of +99.5%,+55.3%, and +21.7% compared to +29.2%,+8.1%, and +6.9% in non-progressors (p < 0.005 for all). Follow-up whole-volume and small-volume ROIs ADC values were significantly reduced in progressors (-11.7% and -9.5%) compared to non-progressors (-6.1% and -1.6%) (p < 0.05 for both). The combined AUC of a relative increase in maximum tumour diameter by 20% and reduction in small-volume ADC by 10% was 0.67. CONCLUSION: AS patients show significant differences in tumour measurements and ADC values between those with and without histopathological disease progression. ADVANCES IN KNOWLEDGE: This paper proposes specific clinical cut-offs for T2WI-derived maximum tumour diameter (+20%) and small-volume ADC (-10%) to predict histopathological PCa progression on AS and supplement subjective serial MRI assessment.