AbstractStandardized reporting of multiparametric prostate MRI (mpMRI) is widespread and follows international standards (Pi-RADS). However, quantitative measurements from mpMRI are not widely comparable. Although T2 mapping sequences can provide repeatable quantitative image measurements and extract reliable imaging biomarkers from mpMRI, they are often time-consuming. We therefore investigated the value of quantitative measurements on a highly accelerated T2 mapping sequence, in order to establish a threshold to differentiate benign from malignant lesions. For this purpose, we evaluated a novel, highly accelerated T2 mapping research sequence that enables high-resolution image acquisition with short acquisition times in everyday clinical practice. In this retrospective single-center study, we included 54 patients with clinically indicated MRI of the prostate and biopsy-confirmed carcinoma (n = 37) or exclusion of carcinoma (n = 17). All patients had received a standard of care biopsy of the prostate, results of which were used to confirm or exclude presence of malignant lesions. We used the linear mixed-effects model-fit by REML to determine the difference between mean values of cancerous tissue and healthy tissue. We found good differentiation between malignant lesions and normal appearing tissue in the peripheral zone based on the mean T2 value. Specifically, the mean T2 value for tissue without malignant lesions was (151.7 ms [95% CI: 146.9–156.5 ms] compared to 80.9 ms for malignant lesions [95% CI: 67.9–79.1 ms]; p < 0.001). Based on this assessment, a limit of 109.2 ms is suggested. Aditionally, a significant correlation was observed between T2 values of the peripheral zone and PI-RADS scores (p = 0.0194). However, no correlation was found between the Gleason Score and the T2 relaxation time. Using REML, we found a difference of -82.7 ms in mean values between cancerous tissue and healthy tissue. We established a cut-off-value of 109.2 ms to accurately differentiate between malignant and non-malignant prostate regions. The addition of T2 mapping sequences to routine imaging could benefit automated lesion detection and facilitate contrast-free multiparametric MRI of the prostate.