Mild to moderate traumatic brain injury (TBI) is associated with increased risk of Post-Traumatic Stress Disorder (PTSD) in returning veterans of the Iraq and Afghanistan wars. Evidence from neuroimaging and neuropsychological studies suggests that PTSD and TBI may share a common neural network, and that disruption of this network may increase the risk of developing PTSD symptoms. The purpose of this study was to investigate the overlapping neuropsychological and neuroanatomical substrates of PTSD and TBI within a sample of veterans. We predicted that both TBI and increasing PTSD symptom severity would be associated with poorer neuropsychological performance, lower integrity of white matter fiber bundles, and thinning of the frontal and temporal cortical regions. A final sample of 38 veterans [ages 21-50; mild: n=33; moderate: n=5)] approximately four years removed from their TBI event(s) were compared to 17 veterans without a history of TBI. Assessments included neuroimaging, cognitive testing, a detailed TBI interview, and the Post-traumatic Stress Disorder Check List-Military Version (PCL-M). Cortical thickness measures were derived from structural MR imaging, and measures of white matter integrity were derived from diffusion tensor imaging. Compared to control participants the TBI group had higher PCL-M scores (p<.01), lower white matter integrity in the cingulum bundle (p<.01) and the genu (p<.05), poorer memory performance and slower processing speed (p's<.05). Slower processing speed was associated with lower white matter integrity across many white matter pathways (p-values ranged from <.001-.05). Higher PCL-M scores were associated with cortical thinning of the left orbitofrontal cortex (p<.05) and unexpectedly with lower diffusion in the fornix (p<.05). The results found little evidence for a disrupted "common network" between TBI and PTSD. Instead, they support unique and non-overlapping effects of TBI and PTSD symptom severity such that TBI is associated with deficits in memory and processing speed, and disrupted frontal white matter myelin integrity, whereas PTSD was associated with thinning of a cortical region associated with emotional regulation. Results suggest that persisting neurocognitive deficits may be associated with TBI-related disrupted myelin integrity to a greater degree than comorbid psychiatric illness.