Bladder cancer is the second most common genitourinary cancer. At the initial diagnosis, one-third of all patients are diagnosed with muscle-invasive bladder cancer (MIBC, stage T2 or greater). MIBC essentially consists of high-grade cancer cells, which require intensive treatments such as radical cystectomy, systemic chemotherapy and radiotherapy, while non-muscle-invasive bladder cancer (stage T1 or less) is conservatively treated using transurethral surgery. However, one-third of high-grade T1 cancer progresses to MIBC or develops metastasis during follow-up. Therefore, the pathological phenotypes are important in managing bladder cancer patients. Diffusion-weighted magnetic resonance imaging (DW-MRI) is a non-invasive functional imaging technique that reveals physiological information by quantifying the diffusion of water molecules in tissues.^1,2 Recently, growing evidence has emerged showing that the DW-MRI signal can be an imaging biomarker for pathophysiological characteristics of the tissue, and the usefulness of DW-MRI has been increasingly shown in characterizing clinical aggressiveness of various malignancies including bladder cancer.^1-5 The extent of restricted water molecule diffusion in tissues can be evaluated as the apparent diffusion coefficient (ADC) value by calculating the signal attenuation on DW-MRI using increasing b-values. Previous studies have showed the feasibility of using ADC values as a quantitative parameter that reflects the characteristics of the bladder cancer.^3-5 It was shown that the ADC value was significantly and inversely correlated with histological grade. However, as an intrinsic limitation, ADC measurements depend on MRI systems and imaging protocols.^1,2 To eliminate this intrinsic limitation of the ADC measurements, standardization of ADC management is required to use the ADC as a clinically applicable biomarker. In the current analysis, we propose a means of standardizing ADC values in bladder cancer by taking the ratio of the ADC value of the cancer tissue to that of the gluteus maximus. We also evaluated that standardized ADC value can be a biomarker for predicting histological grade under two different imaging conditions.Two independent bladder cancer cohorts including 107 patients at Tokyo Medical and Dental University Hospital (TMDU), Tokyo, Japan and 47 patients at Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital (CICK), Tokyo, Japan, who underwent MRI before the treatment intervention, were retrospectively evaluated. In patients with multiple tumors, only the index tumor was evaluated in the current analysis. All the tumors included were histopathologically diagnosed as urothelial carcinoma. The ADC value of the index tumor and the gluteus maximus were calculated on an ADC map. A region of interest (ROI) was manually drawn to maximally cover the index tumor on the transverse ADC map at the slice that showed largest tumor diameter. Another ROI with a square of 5 cm² was set within the gluteus maximus. The ADC value of all the pixels within each ROI was quantified, and their mean value was used. The ADC values of the index tumor (T-ADC) and the gluteus maximus (G-ADC), and the ratio of A-ADC to G-ADC (ADC ratio) were compared according to histological grade. The images were acquired using a 1.5 Tesla imager (Intera Achieva; Philips, Best, Netherlands) at TMDU and a 3.0 Tesla imager (Magnetom Skyla; Siemens, Berlin, Germany) at CICK.There was a significant difference in T-ADC and G-ADC between TMDU and CICK (median, 0.89 vs. 1.21 x 10^-3 mm²/sec, and 0. 79 vs. 1.27 x 10^-3 mm²/sec, respectively; P < 0.0001 for both), but no significant difference in the ADC ratio was observed (0.92 vs. 0.92 x 10^-3 mm²/sec). The ADC ratio of grade 3 cancers was significantly lower than that of grade 1/2 cancers (0.85 vs. 1.11 x 10^-3 mm²/sec at TMDU, P = 0.0046; 0.93 vs. 1.06 x 10^-3 mm²/sec at CICK, P = 0.0001), as was the A-ADC value. The best cut-off for the ADC ratio to differentiate grade 3 cancer, assessed in the CICK cohort, was 1.03, and the predictability validation, performed in the TMDU cohort, yielded accuracy/sensitivity/specificity of 74%/86%/47%.The current analysis showed that the ratio of ADC value of the bladder cancer to that of the gluteus maximus, was similar between the two cohorts with different imaging conditions, but there was a large difference in the T-ADC values. The significant association between histological grade and the ADC ratio of the bladder cancer was shown in both cohorts, and the predictability was confirmed through our validation. These results suggested that the T-ADC value without any corrections should not be used in the inter-institutional study, and the usefulness of ADC value standardization using the ADC ratio for predicting histological cancer grade needs to be further validated in a multi-center analysis.Use of the ADC ratio for standardization to the gluteus maximus may mitigate inter-institutional disparity. The standardized ADC might serve as an inter-institutional biomarker for predicting histological cancer grade in patients with bladder cancer.