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Patients with traumatic brain injuries (TBIs) are at high risk for venous thromboembolic sequelae; however, prophylaxis is often delayed because of the perceived risk of intracranial hemorrhagic exacerbation. The goal of this study was to determine whether enoxaparin for early venous thromboembolism (VTE) prophylaxis is safe for hemodynamically stable patients with TBIs.This is a retrospective cohort study from a Level I Trauma Center of patients with TBIs receiving early (0–72 hours) or late (>72 hours) VTE prophylaxis. Inclusion criteria included evidence of acute intracranial hemorrhagic injury (IHI) on admission computed tomography, head/neck abbreviated injury score ≥3, age ≥16 years, and hospital length of stay ≥72 hours. Exclusion criteria included intracranial pressure monitor/ventriculostomy, current systemic anticoagulation, pregnancy, coagulopathy, history of DVT, ongoing intra-abdominal hemorrhage 24 hours postadmission, and preexisting inferior vena cava filter. Progression of IHI defined as lesion expansion/new IHI on repeat computed tomography.Totally, 669 patients were identified: 268 early (40.1%) and 401 late (59.9%), with a mean injury severity score of 27.8 ± 10.2 and 29.4 ± 11, respectively. Head neck abbreviated injury score of 3 (47% vs. 34%), 4 (42% vs. 46%), 5 (11% vs. 19%), and 6 (0% vs. 1%) were reported for the early and late treatment groups, respectively. Mean time to prophylaxis was 2.77 days ± 0.49 days and 5.31 days ± 1.97 days. IHI progression before prophylaxis was 9.38% versus 17.41% (p < 0.001) and after prophylaxis was 1.46% versus 1.54% (p > 0.9). Proportions of proximal DVT were 1.5% versus 3.5% (p = 0.117) and pulmonary embolism were 1.5% versus 2.2% (p = 0.49). There were no differences in injury severity score, age, and pelvic and/or long bone fractures.We found no evidence that early VTE prophylaxis increases the rate of IHI progression in hemodynamically stable patients with TBIs. The natural rate of IHI progression observed is comparable with previous studies. Although not powered to detect differences in the incidence of DVT and pulmonary embolism, the data trend toward increased proportions of both VTE outcomes in the late group.