INTRODUCTION: Deep venous thrombosis (DVT) is common among trauma patients. If left untreated it may result in lethal pulmonary thromboembolism. Previous studies have suggested that intracranial hemorrhage serves as an independent risk factor for the development of DVT. These studies were not able to exclude anticoagulation therapy as a confounding variable in their analysis. Our objective was to determine the association of traumatic brain injury (TBI) to the formation of DVT irrespective of the use of anticoagulation therapy. METHODS: All patients admitted to an academic level I Trauma Center between 2000 and 2007 with blunt or penetrating injuries were selected for inclusion in this study. Patients who died or who were discharged within 24 hours of admission were excluded in the analysis. TBI was defined as any intraparenchymal hemorrhage or extra-axial intracranial bleeding identified on radiographic imaging or both. Anticoagulation therapy was defined as the uninterrupted use of either subcutaneous lovenox or heparin. Risk ratios and 95% confidence intervals compared the risk of DVT among patients with and without TBI according to the initiation of anticoagulation therapy (no therapy, <24 hours, 24-48 hours, and >48 hours) adjusted for age, gender, race, injury severity, mechanism of injury, spinal injury, and lower extremity fracture. RESULTS: Irrespective of the time of initiation of pharmacologic prophylaxis, TBI is independently associated with the formation of DVT. A threefold to fourfold increased risk of DVT formation is consistent across all prophylaxis groups among patients with TBI. CONCLUSION: The incidence of DVT among injured patients with TBI is significantly higher than those patients without head injury independent of anticoagulation therapy. Rigorous surveillance to detect DVT among trauma patients with TBI should be undertaken and where appropriate alternate means for pulmonary thromboembolism prevention used.