Background A readily implemented MRI biomarker for glioma genotyping is currently lacking. Purpose To evaluate clinically available MRI parameters for predicting isocitrate dehydrogenase ( ) status in patients with glioma. Materials and Methods In this retrospective study of patients studied from July 2008 to February 2019, untreated World Health Organization (WHO) grade II/III gliomas were analyzed by three neuroradiologists blinded to tissue results. Apparent diffusion coefficient (ADC) minimum (ADC ) and mean (ADC ) regions of interest were defined in tumor and normal appearing white matter (ADC ). A visual rating of anatomic features (T1 weighted, T1 weighted with contrast enhancement, T2 weighted, and fluid-attenuated inversion recovery) was performed. Interobserver comparison (intraclass correlation coefficient and Cohen κ) was followed by nonparametric (Kruskal-Wallis analysis of variance) testing of associations between ADC metrics and glioma genotypes, including Bonferroni correction for multiple testing. Descriptors with sufficient concordance (intraclass correlation coefficient, >0.8; κ > 0.6) underwent univariable analysis. Predictive variables ( < .05) were entered into a multivariable logistic regression and tested in an additional test sample of patients with glioma. Results The study included 290 patients (median age, 40 years; interquartile range, 33-52 years; 169 male patients) with 82 wild-type, 107 mutant/1p19q intact, and 101 mutant/1p19q codeleted gliomas. Two predictive models incorporating ADC -to-ADC ratio, age, and morphologic characteristics, with model A mandating calcification result and model B recording cyst formation, classified tumor type with areas under the receiver operating characteristic curve of 0.94 (95% confidence interval CI: 0.91, 0.97) and 0.96 (95% CI: 0.93, 0.98), respectively. In the test sample of 49 gliomas (nine wild type, 21 mutant/ intact, and 19 mutant/ codeleted), the classification accuracy was 40 of 49 gliomas (82%; 95% CI: 71%, 92%) for model A and 42 of 49 gliomas (86%; 95% CI: 76%, 96%) for model B. Conclusion Two algorithms that incorporated apparent diffusion coefficient values, age, and tumor morphologic characteristics predicted isocitrate dehydrogenase status in World Health Organization grade II/III gliomas on the basis of standard clinical MRI sequences alone. © RSNA, 2020