Moderate and severe traumatic brain injuries (TBI) are life-threatening, necessitating prompt evaluation and intervention. The safe air transport of patients with TBI to a higher level of care requires additional considerations. Patients with TBI are susceptible to complications related to altitude, including hypobaria and hypoxia. To mitigate this risk, some patients are transported with a cabin altitude restriction (CAR), which limits the altitude at which an aircraft’s cabin is maintained. The goal of this study was to examine the effects of altitude and oxygenation on patients with TBI transported via critical care air transport teams (CCATT) from a Role III medical treatment facility (MTF) to Landstuhl Regional Medical Center (LRMC). We conducted a retrospective chart review of patients with moderate to severe TBI evacuated out of combat theater via CCATT. Data abstractors collected data on demographics, flight information (including CAR), injury type, injury severity, pre-flight procedures, in-flight oxygenation, in-flight complications, and outcomes (mortality, hospital days, ICU days, and ventilator days). We calculated descriptive statistics and conducted Cox proportional hazards regression analyses to evaluate the association between CAR and clinical outcomes. We reviewed the CCATT charts of 435 patients with TBI transported via CCATT from a Role III MTF to LRMC. Eighty-one patients (19%) had a recorded CAR. About 19% of the sample had a PaO2 lower than 80 mmHg and 5% of patients experienced an in-flight SpO2 of 93% or lower. Flying without a CAR was not significantly associated with increased mortality or more hospital days, ICU days, or ventilator days. Further, having a CAR was not significantly associated with hospital days, ICU days, or ventilator days after adjusting for additional flights, injury severity, and injury type. Patients with moderate or severe TBI who were flown with a recorded CAR did not significantly differ from those who flew without a CAR in mortality rates, hospital days, ICU days, or ventilator days. Funding support: Air Force Medical Service (AFMS) Disclaimer: The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Air Force, Department of the Army, Department of Defense, or US Government.