Purpose To analyze if fractional anisotropy (FA) in nonenhancing peritumoral regions (NEPTRs) at baseline is associated with later tumor recurrence in glioblastoma. Materials and Methods Ethical approval was obtained for this retrospective, HIPAA-compliant study. FA was measured in 70 patients with glioblastoma in five regions of interest (ROIs) per patient in the NEPTR at preoperative magnetic resonance (MR) imaging with (166 regions) or without (184 regions) local contrast-enhancing tumor recurrence at follow-up MR imaging (median, 7.3 months; range, 0.9-46.6 months). ROIs were classified according to their location (white matter, cortex, fiber tracts, basal ganglia). Ratio of FA in the ROI of the NEPTR to that in the contralateral side (FAcontra) and to that in the internal capsule (FAint) was calculated. A generalized linear mixed model was performed. Ten-fold cross-validation was used for the receiver operating characteristics (ROC) analysis. Results FAcontra and FAint were significantly lower in regions with later tumor recurrence than in regions without (median FAcontra: 0.29 [interquartile range {IR}, 0.22-0.36] vs 0.46 [IR, 0.38-0.57]; median FAint: 0.20 [IR, 0.16-0.24] vs 0.29 [IR, 0.22-0.36], respectively). ROC analysis revealed an area under the ROC curve of 0.893 for FAcontra and of 0.815 for FAint, resulting in respective sensitivity and specificity of 85.5% and 84.2% for FAcontra and 86.7% and 66.8% for FAint. Conclusion Local tumor recurrence in the NEPTR may be predicted by FA metrics at baseline in patients with glioblastoma. This might be important for surgery or radiation planning. © RSNA, 2016 Online supplemental material is available for this article.