Objective: To evaluate whether diffusion tensor imaging (DTI) will noninvasively reveal white matter changes not present on conventional MRI in acute blast-related mild traumatic brain injury (mTBI) and to determine correlations with clinical measures and recovery.Methods: Prospective observational study of 95 US military service members with mTBI enrolled within 7 days from injury in Afghanistan and 101 healthy controls. Assessments included Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ), Post-Traumatic Stress Disorder Checklist Military (PCLM), Beck Depression Inventory (BDI), Balance Error Scoring System (BESS), Automated Neuropsychological Assessment Metrics (ANAM), conventional MRI, and DTI.Results: Significantly greater impairment was observed in participants with mTBI vs controls: RPCSQ (19.7 6 12.9 vs 3.6 6 7.1, p , 0.001), PCLM (32 6 13.2 vs 20.9 6 7.1, p , 0.001), BDI (7.4 6 6.8 vs 2.5 6 4.9, p , 0.001), and BESS ( Conclusions: Somatic, behavioral, and cognitive symptoms and performance deficits are substantially elevated in acute blast-related mTBI. Postconcussive symptoms and performance on measures of posttraumatic stress disorder, depression, and neurocognitive performance at initial presentation correlate with return-to-duty time. Although changes in fractional anisotropy are uncommon and subtle, DTI is more sensitive than conventional MRI in imaging white matter integrity in blast-related mTBI acutely. Blast-related mild traumatic brain injury (mTBI) has emerged as one of the most prevalent war injuries sustained by service members in the conflicts in Afghanistan and Iraq.