Patients requiring reintubation after failed extubation have a poor prognosis, with hospital mortality exceeding 30 to 40%, though the reason remains unclear. To examine the impact of etiology of extubation failure and time to reintubation on hospital outcome, we performed a post hoc analysis of prospectively gathered data on 74 MICU patients (47 men, 27 women), 64 +/- 2 yr of age who required reintubation within 72 h of extubation. Cause for reintubation was classified as airway (upper airway obstruction, 11; aspiration/excess pulmonary secretions, 12) or nonairway (respiratory failure, 21; congestive heart failure, 17; encephalopathy, 7; other, 6). The duration of mechanical ventilation prior to extubation was 139 +/- 19 h, and the median time to reintubation was 21 h. Thirty-one of 74 patients (42%) died, with mortality highest for patients failing from nonairway etiologies (27/51, 53% versus 4/23, 17%; p < 0.01). Patients failing from an airway cause tended to be reintubated earlier (21 +/- 4 versus 31 +/- 3 h, p = 0.07). Mortality increased with longer duration of time from extubation to reintubation (<= 12 h, 6/25 versus > 12 h, 25/49; p < 0.05). With multiple logistic regression, both cause for extubation failure and time to reintubation were independently associated with hospital mortality. In conclusion, etiology of extubation failure and time to reintubation are independent predictors of outcome in reintubated MICU patients. The high mortality for those reintubated for nonairway problems indicate that efforts should be preferentially focused on identifying these patients. The effect of time to reintubation suggests that identification of patients early after extubation and timely reinstitution of ventilatory support has the potential to reduce the increased mortality associated with extubation failure.