Objectives: To determine perioperative predictors of extubation failure (requirement for reintubation and mechanical ventilation after prior successful weaning from ventilator support and extubation) after cardiac surgery and the effect on clinical outcome. Design: Cohort study. Setting: A tertiary care, 54 bed, cardiothoracic intensive care unit (ICU). Patients: ICU admissions (n =11,330) after cardiac surgery over a 42-month period. Interventions: Collection of preoperative, operative, and ICU data from a database, Measurements and Main Results: Frequency of extubation failure, total duration of mechanical ventilation, length of stay in ICU and hospital, and death. There were 748 (6.6%) patients who were weaned from mechanical ventilation after cardiac surgery and required reintubation and ventilator support, The predictors of extubation failure were: age of greater than or equal to 65 yrs; inpatient hospitalization before surgery; arterial vascular disease; chronic obstructive pulmonary disease; pulmonary hypertension; severe left Ventricular dysfunction; cardiac shock; hematocrit of less than or equal to 34%; blood urea nitrogen of greater than or equal to 24 mg/dL; serum albumin concentration of less than or equal to 4.0 g/dL (less than or equal to 40.0 g/L); systemic oxygen delivery of less than or equal to 320 mL/min/m(2); redo operation; surgical procedures involving the thoracic aorta; transfusion of blood products of greater than or equal to 10 units; and cardiopulmonary bypass time of greater than or equal to 120 mins, Extubation failure prolonged the length of total mechanical ventilation, as well as ICU and hospital stay, independent of the frequency of organ dysfunction or nosocomial infections but did not increase the risk of death after cardiac surgery. Conclusions: Extubation failure after cardiac surgery is un common. Although extubation failure increased the utilization of ICU and hospital resources, it did not affect mortality after cardiac surgery, Protocols for early extubation and ICU discharge should be modified in the presence of certain preoperative and operative predictors of extubation failure to avoid unnecessary increase in the cost of care after cardiac surgery.