This study was performed to determine if prolonged mechanical ventilation (MV) could be predicted by objective clinical variables present at 48 hours after MV was instituted. During a 3-month period, 49 (54%) of 91 mechanically ventilated surgical intensive care unit patients required MV for 2 or more days. Twelve (24%) of these patients died. Patients requiring 2-13 days of MV had significantly lower alveolar-arterial oxygen gradients (PAO2 - PAO2), PEEP, and FIO2 on MV day 2 compared with patients with MV greater than or equal to 14 days. PAO2 - PAO2 greater than or equal to 175 mm Hg on day 2 in patients without chronic obstructive pulmonary disease (COPD) was 60% sensitive and 91% specific for MV greater than or equal to 14 days. In survivors, a day-2 PAO2 - PAO2 greater than or equal to 175 mm Hg (without COPD) or a GCS score less than or equal to 9 had a 91% positive predictive value and a 96% negative predictive value for MV greater than or equal to 14 days. We conclude that mechanical ventilation for 14 or more days can be accurately predicted at 48 hours after the institution of ventilatory support by these objective criteria.