Lung repair after diffuse alveolar damage (DAD) may be modified by supportive therapy or the occurrence of complications. To provide a clinically relevant model of DAD, we studied the feasibility of long-term respiratory support of 5 normal baboons and 20 baboons with oleic-acid-induced lung injury. Oleic acid caused DAD, which evolved through exudative and reparative phases similar to those seen in human disease. Fibrotic residuals were present at 1 month but resolved by 6 months. Pulmonary function abnormalities, including reduction in total lung capacity and diffusing capacity, and hypoxemia occurred with DAD but resolved within 1 month. Bronchopulmonary infection with gram-negative bacilli was a common and frequently fatal complication. Revisions in management of the upper airway and the use of topical polymyxin B prevented this complication. Other complications included hemorrhagic gastritis, postextubation, upper airway obstruction, and pulmonary embolism. This model simulates many features of DAD in humans and should provide a valuable resource for future study.