Brain lesions after traumatic brain injury (TBI) are heterogeneous, rendering outcome prognostication difficult. The aim of this study is to investigate whether early magnetic resonance imaging (MRI) of lesion location and lesion volume within discrete brain anatomical zones can accurately predict long-term neurological outcome in children post-TBI. Fluidattenuated inversion recovery (FLAIR) MRI hyperintense lesions in 63 children obtained 6.2 -5.6 days postinjury were correlated with the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score at 13.5 -8.6 months. FLAIR lesion volume was expressed as hyperintensity lesion volume index (HLVI) = (hyperintensity lesion volume / whole brain volume) · 100 measured within three brain zones: zone A (cortical structures); zone B (basal ganglia, corpus callosum, internal capsule, and thalamus); and zone C (brainstem). HLVI-total and HLVI-zone C predicted good and poor outcome groups ( p < 0.05). GOS-E Peds correlated with HLVI-total (r = 0.39; p = 0.002) and HLVI in all three zones: zone A (r = 0.31; p < 0.02); zone B (r = 0.35; p = 0.004); and zone C (r = 0.37; p = 0.003). In adolescents ages 13-17 years, HLVItotal correlated best with outcome (r = 0.5; p = 0.007), whereas in younger children under the age of 13, HLVI-zone B correlated best (r = 0.52; p = 0.001). Compared to patients with lesions in zone A alone or in zones A and B, patients with lesions in all three zones had a significantly higher odds ratio (4.38; 95% confidence interval, 1.19-16.0) for developing an unfavorable outcome.