Of 210 multiple trauma patients admitted to our Intensive Care Unit (ICU), 12 (5%) presented with severe hypoxemic respiratory failure needing mechanical ventilation with an FIO2of 1.0 because of severe intrapulmonary shunting (IS). Five (42%) of these patients survived and two (17%) died because of their underlying respiratory failure. We found a mean of three etiologic factors in each patient to account for their IS. Nonsurvivors had a lower cardiac index than survivors when they first needed FIO2of 1.0 and ARDS was more frequent among this group. All patients who survived were in severe hypoxemic respiratory failure in the first 5 days post-trauma; all patients who needed FIO2of 1.0 later than 5 days post-trauma died. Data collected for patients with similar degree of respiratory failure in coronary care ICU (n= 18), in medical ICU (n= 19), and surgical ICU (n= 21) demonstrated that multiple trauma patients with severe hypoxemic respiratory failure were younger and were hospitalized and ventilated for longer periods of time. In multiple trauma patients, as for patients with cardiogenic pulmonary edema, death was seldom related to respiratory failure itself. We concluded that severe hypoxemic respiratory failure in trauma patients is usually of mixed etiologies. It is a serious cause of morbidity in these patients; however, mortality is seldom directly related to this condition. Severe IS occurring shortly after trauma is of better prognosis than late IS.