Glioma cells may infiltrate beyond the tumor margins revealed on conventional structural images. To investigate whether the presence of a glioma infiltration sign on high b-value diffusion-weighted imaging (DWI) can predict the prognosis of gliomas. Retrospective cohort. Fifty-two patients with gliomas (14 WHO grade II; 13 WHO grade III; 25 WHO grade IV). 3.0T, including a T1 -weighted contrast-enhanced (T1 w-CE) sequence, contrast-enhanced T2 -flair sequence, and a DWI sequence. T1 w-CE images and contrast-enhanced T2 -flair images were used for identifying the tumor region for enhancing and nonenhancing gliomas, respectively. The glioma infiltration sign was defined as the presence of a peritumoral abnormal high signal region on DWI map, which was adjacent to the tumor region and had higher signal than surrounding areas. This sign was assessed on a high b-value DWI map with b = 3000 s/mm2 . For patients with glioma infiltration sign, DWI3000max , DWI1000max , ADC3000min , and ADC1000min were measured by drawing a region of interest over the peritumoral abnormal high signal region. Survival analysis was conducted by using Cox regression. Glioma infiltration sign was observed in 28 (53.8%) patients. The occurrence rate of this sign was 92.0% in grade IV gliomas, 30.8% in grade III gliomas, and 7.1% in grade II gliomas. The glioma infiltration sign could independently predict both the progression-free survival (hazard ratio [HR], 95% confidence interval [CI] = 8.58 [3.19-23.03], P < 0.001) and overall survival (HR, 95% CI = 11.90 [3.41-41.55], P < 0.001) after adjustment. For patients with glioma infiltration sign, DWI3000max (P = 0.005) and ADC3000min (P = 0.008) were both independent predictors of overall survival after adjustment, while DWI1000max and ADC1000min were not. The glioma infiltration sign on high b-value DWI is an independent predictor of poor prognosis in glioma patients. High b-value DWI might be a convenient method to detect glioma infiltration. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.