The purpose of the present study was to investigate the prognostic role of severe hypoxemia on admission as an independent risk factor of pulmonary complications and mortality in patients with acute pancreatitis. Pulmonary complications were studied in 166 previously healthy patients with acute pancreatitis. Forty-eight patients (28.9%) developed one or more pulmonary complications, including pleural effusion, atelectasis, pulmonary consolidations, and acute respiratory distress syndrome (ARDS). Pulmonary consolidations (odds ratio = 7.25) and, especially, ARDS (odds ratio = 22.9) were significantly associated with severe baseline hypoxemia (PaO2, <60 mm Hg). Mortality was mainly related to severity of disease (odds ratio = 46.45), while hypoxemia was also found to be an independent risk factor of poor outcome (odds ratio = 9.56). It seems that, in patients with acute pancreatitis, severe hypoxemia on admission may be an early predictive marker of pulmonary complications, especially ARDS, and, independently of severity score, it may also be a marker of poor outcome.