Inhalation injury predisposes burn patients to pneumonia, respiratory failure, and death, but the incidence and consequences of respiratory failure in the absence of inhalation injury are not well known. In a review of 529 burn patients admitted over a 4-year period, patients with inhalation injury had a 73% incidence of respiratory failure (hypoxemia, multiple pulmonary infections, or prolonged ventilator support) and a 20% incidence of adult respiratory distress syndrome (ARDS). In patients without inhalation injury, respiratory failure developed in 5% of patients and ARDS in 2% (both p < 0.001). Patients with respiratory failure display a high incidence of multiple organ failure and mortality (27% to 50%), regardless of the presence of inhalation injury. All patients who died had multiple organ failure. This review demonstrates that respiratory failure, regardless of its cause, frequently leads to multiple organ failure and death. Inhalation injury, in the absence of respiratory failure, does not appear to contribute to mortality.