Unplanned extubation is a major complication of translaryngeal intubation, but its impact on mortality, duration of mechanical ventilation (MV), length of intensive care unit (ICU) and hospital stay, and need for ongoing hospital care has not been adequately defined. We performed a case-control study in a tertiary-care medical ICU, comparing 75 patients with unplanned extubation and 150 controls matched for Acute Physiology and Chronic Health Evaluation II score, presence of comorbid conditions, age, indication for MV, and sex. Forty-two (56%) patients required reintubation after unplanned extubation (74% immediately, 86% within 12 h). Thirty-three (44%) unplanned extubations occurred during weaning trials, and 30% of these patients needed reintubation (failed unplanned extubation). In contrast, 76% of patients with unplanned extubation occurring during ventilatory support required reintubation. Although mortality was similar to that of controls (failed unplanned extubation 40%, versus control 31%, p > 0.2), patients with failed unplanned extubation had a significantly longer duration of MV (19 versus 11 d, p < 0.01), longer stay in the ICU (21 versus 14 d, p < 0.05), and longer hospital stay (30 versus 21 d, p < 0.01), and survivors were more likely to require chronic care (64% versus 24%, p < 0.001). Successfully tolerated unplanned extubation was associated with a reduction in time from beginning of weaning to extubation (0.9 versus 2.0 d, p = 0.06), but with no difference in overall duration of MV, mortality, discharge location, ICU, or hospital stay as compared with these measures for controls. We conclude that unplanned extubation is not associated with increased mortality when compared with that of matched controls, although it does result in prolonged MV, longer ICU and hospital stay, and increased need for chronic care. These effects are due exclusively to patients who fail to tolerate unplanned extubation. Although successfully tolerated unplanned extubation decreased the duration of weaning trials, it had no other measurable beneficial impact on outcome.