The hemodynamic response (HDR) function is the basis for standard functional magnetic resonance imaging (fMRI) analysis. HDR is influenced by white matter inflammation. Traumatic brain injury (TBI) is frequently accompanied by diffuse white matter injury, but the effect of this on the HDR has not been investigated. The aims of the present study were to describe the HDR in visual cortex and examine its relationship with the microstructure of the optic radiation in severe TBI survivors and controls. Ten severe TBI survivors without visual impairments, but with known diffuse axonal injury, and 9 matched controls underwent diffusion tensor imaging (DTI) and fMRI. From the fMRI time series obtained during brief randomized visual stimuli, blood oxygenation level-dependent (BOLD) signal changes for each subject were estimated in V1, and group HDR curves were produced. Standard between-group analysis of BOLD activation in V1 + V2 was performed. For each individual the optic radiations were identified and fractional anisotropy (FA) plus mean apparent diffusion coefficient (ADC(mean)) values for these tracts were calculated. Group HDR curves from the visual cortex were fully transposable between TBI survivors and controls, despite a significant reduction in FA in the optic radiation in TBI survivors. A significant correlation between BOLD signal in the visual cortex and FA values in the optical tract was present in controls, but not in TBI survivors. Between-group comparisons showed that TBI survivors had increased areas of activation in V1 and V2. The HDR appears to be intact in traumatic white matter damage, supporting the validity of using standard fMRI methodology to study neuroplasticity in TBI.