The influence of delirium, ICU-acquired paresis, and cardiac performance on extubation outcome has never been evaluated together. We aimed to assess the respective role of these factors on the risk of extubation failure and to assess the predictive accuracy of caregivers.Prospective observational study of all planned extubations in a 13-bed medical ICU of a teaching hospital.On the day of extubation, muscle strength of the four limbs, criteria for delirium, cardiac performance, cough strength, and the risk of extubation failure predicted by caregivers were prospectively assessed. Extubation failure was defined as the need for reintubation within the following 7 days.Over the 18-month study period, 533 patients required intubation. Among the 225 patients intubated for more than 24 hours who experienced a planned extubation attempt, 31 patients (14%) required reintubation within the 7 days following extubation. In multivariate analysis, duration of mechanical ventilation more than 7 days prior to extubation, ineffective cough, and severe systolic left ventricular dysfunction were the three independent factors associated with extubation failure. Although patients considered at high risk for extubation failure had higher reintubation rate, prediction of extubation failure by caregivers at time of extubation had high specificity but low sensitivity.An ineffective cough, a prior duration of mechanical ventilation more than 7 days, and severe systolic left ventricular dysfunction were stronger predictors of extubation failure than delirium or ICU-acquired weakness. Only one-third patients who required reintubation were considered at high risk for extubation failure by caregivers.