Objective This clinical study analyzed the mortality rates and analyzed the risk factors for mortality in high-altitude patients with severe traumatic brain injury.Methods We retrospectively reviewed the medical records of 367 high-altitude patients with severe traumatic brain injury at the General Hospital of Tibetan Military Region from June 2007 to June 2012. Multivariate Logistic regression analysis was used to evaluate the influence of clinical variables on mortality at 3 months after admission.Results The overall mortality was 22% (80/367) at 3 months. The time from trauma to admission (OR=1.805), initial Glasgow Coma Score (OR=1.991), pupillary response (OR=2.033) and midline shift (OR=1.717) were independent risk factors for death, while no significant association was observed between the mortality rate and the gender, age or altitude of patients.Conclusions This study identified the risk factors for mortality in high-altitude patients with severe traumatic brain injury. The higher risk of death occurs in patients with longer intervals between trauma and admission, lower initial Glasgow Coma Scores, bilateral pupil dilatation and a Midline shift more than 10 mm on initial CT scan. The findings should help clinicians determine management criteria and improve survival.