OBJECTIVE: This study aimed to assess any correlation between serum levels of homocysteine (Hcy) and markers of cerebral hemodynamics, endothelial dysfunction, and cognition impairment in patients with traumatic brain injury (TBI). METHODS: By a cross-sectional study, all clinical data and serum levels of homocysteine of 85 TBI patients were collected. The pulsatility indices (PIs) of the middle cerebral artery were recorded by transcranial color-coded Doppler ultrasonography and cerebrovascular reactivity was measured by the increase in middle cerebral artery flow velocity in response to 5% inhaled CO2. Serum levels of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1), cognition status by Montreal Cognitive Assessment, and Mini-Mental State Examination were measured in all participants. RESULTS: Totally, 85 patients including 51.76% male and the mean age of 54.48 years were studied. The level of Hcy in patients who died in the hospital or during 6 months after TBI was significantly higher than in survivors (P = 0.045, P = 0.020, respectively). Also, the levels of ICAM-1, VCAM-1, and PI in deceased patients were higher than their figures in survivors in both hospital and 6-month follow-ups (P = 0.450, P = 0.000; P = 0.072, P = 0.000, P = 0.090, and P = 0.000, respectively). Cerebrovascular reactivity in deceased patients was significantly lower than that in alive individuals (P = 0.008 and P = 0.000, respectively). A significant correlation was found between Hcy with cognition impairment according to Montreal Cognitive Assessment, Mini-Mental State Examination, and cerebral hemodynamic status according to PI (P = 0.000 for all). Also, this correlation was shown between Hcy with ICAM-1 and VCAM-1 in hospital and 6-month follow-ups (P = 0.000 for both). CONCLUSION: Hcy has a significant correlation with markers of cerebrovascular, endothelial, and cognition abnormality in TBI patients.