Introduction: Extubation failure is said to be associated with increased morbidity and mortality. Patients and methods: This was a prospective, observational study of extubation failure among all patients who have been intubated and required ventilatory support in the Multi-Disciplinary Intensive Care Unit (MICU) of Kasturba Hospital, Manipal from 1st September 2007 to 30th September 2008. Criteria for considering extubation failure were similar to those used to evaluate need for intubation. Results: Of 167 patients who received invasive ventilation through an oral endotracheal tube, 145 were extubated successfully and 22 patients failed extubation. They were managed either with noninvasive ventilation (NIV) or reintubation as decided by the physician. The incidence of extubation failure was 13.1%. Only one patient could be managed with NIV. One was discharged against medical advice. Of the twenty patients who were reintubated, seven patients could be reextubated, seven required tracheostomy and six died. A mortality rate of 33% was observed in these patients. Extubation failure was mainly due to respiratory causes (15/21 patients), most of whom (11/15 patients) survived. Those due to nonrespiratory causes (6/15 patients) had 50% survival. The mean duration of mechanical ventilation prior to extubation was significantly lower among survivors (56 ± 25.1 hours) but the total duration of mechanical ventilation and ICU stay were not very different. Conclusions: Extubation failure is associated with high mortality. Extubation failure occurs most often due to respiratory causes and noninvasive positive pressure ventilation is not useful for patients who fail extubation.