To evaluate the feasibility of high b-value diffusion-weighted imaging (DWI) for distinguishing non-muscle-invasive bladder cancer (NMIBC) from muscle-invasive bladder cancer (MIBC) and low- from high-grade bladder urothelial carcinoma using a fractional-order calculus (FROC) model as well as a combination of FROC DWI and bi-parametric Vesical Imaging-Reporting and Data System (VI-RADS).Fifty-eight participants with bladder urothelial carcinoma were included in this IRB-approved prospective study. Diffusion-weighted images, acquired with 16 b-values (0-3600 s/mm2), were analyzed using the FROC model. Three FROC parameters, D, β, and μ, were used for delineating NMIBC from MIBC and for tumor grading. A receiver operating characteristic (ROC) analysis was performed based on the individual FROC parameters and their combinations, followed by comparisons with apparent diffusion coefficient (ADC) and bi-parametric VI-RADS based on T2-weighted images and DWI.D and μ were significantly lower in the MIBC group than in the NMIBC group (p = 0.001 for each), and D, β, and μ all exhibited significantly lower values in the high- than in the low-grade tumors (p ≤ 0.011). The combination of D, β, and μ produced the highest specificity (85%), accuracy (78%), and the area under the ROC curve (AUC, 0.782) for distinguishing NMIBC and MIBC, and the best sensitivity (89%), specificity (86%), accuracy (88%), and AUC (0.892) for tumor grading, all of which outperformed the ADC. The combination of FROC parameters with bi-parametric VI-RADS improved the AUC from 0.859 to 0.931.High b-value DWI with a FROC model is useful in distinguishing NMIBC from MIBC and grading bladder tumors.• Diffusion parameters derived from a FROC diffusion model may differentiate NMIBC from MIBC and low- from high-grade bladder urothelial carcinomas. • Under the condition of a moderate sample size, higher AUCs were achieved by the FROC parameters D (0.842) and μ (0.857) than ADC (0.804) for bladder tumor grading with p ≤ 0.046. • The combination of the three diffusion parameters from the FROC model can improve the specificity over ADC (85% versus 67%, p = 0.031) for distinguishing NMIBC and MIBC and enhance the performance of bi-parametric VI-RADS.© 2021. European Society of Radiology.