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To understand the relations of mild traumatic brain injury (TBI), blast exposure, and brain white matter structure to severity of posttraumatic stress disorder (PTSD).Nested cohort study using multivariate analyses.Fifty-two OEF/OIF veterans who served in combat areas between 2001 and 2008 were studied approximately 4 years after the last tour of duty.PTSD Checklist-Military; Combat Experiences Survey, interview questions concerning blast exposure and TBI symptoms; anatomical magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI) scanning of the brain.PTSD severity was associated with higher 1st percentile values of mean diffusivity on DTI (regression coefficient [r] = 4.2, P = .039), abnormal MRI (r = 13.3, P = .046), and the severity of exposure to combat events (r = 5.4, P = .007). Mild TBI was not significantly associated with PTSD severity. Blast exposure was associated with lower 1st percentile values of fractional anisotropy on DTI (odds ratio [OR] = 0.38 per SD; 95% confidence interval [CI], 0.15–0.92), normal MRI (OR = 0.00, 95% likelihood ratio test CI, 0.00–0.09), and the severity of exposure to traumatic events (OR = 3.64 per SD; 95% CI, 1.40–9.43).PTSD severity is related to both the severity of combat stress and underlying structural brain changes on MRI and DTI but not to a clinical diagnosis of mild TBI. The observed relation between blast exposure and abnormal DTI suggests that subclinical TBI may play a role in the genesis of PTSD in a combat environment.