Body weight is associated with different physiological changes and the association between weight and mortality in critical care setting had been discussed before. In this study, we investigated the linkage between underweight and post-extubation failure in mechanical ventilated patients in critical setting. This is a retrospective cohort study including patients who were admitted to medical or surgical intensive care units (ICU) between June 2016 and July 2018 and had received endotracheal intubation for more than 72 hours. Those who passed spontaneous breathing trial and underwent a planned extubation were enrolled. Extubation failure was defined as those who required reintubation within the first 72 hours for any reasons. The probability of extubation failure was calculated. Demographic and clinical characteristics were recorded. Multivariate logistic regression models were then used to determine the potential risk factors associated with extubation failure. Overall, 268 patients met the inclusion criteria and were enrolled in our study for analysis. The median age of included patients was 67 years (interquartile range, 55-80 years) with 65.3% being male; 63.1% of the patients were included from medical ICU. The proportion of extubation failure in our cohort was 7.1% (19/268; 95% confidence interval [CI], 4.3-10.9%). Overall, underweight patients had the highest risk of extubation failure (8/50), as compared with normoweight (9/135) and overweight patients (2/83). In the multivariate analysis, being underweight (adjust OR [aOR], 3.80, compared to normoweight; 95% CI, 1.23-11.7) and lower maximal inspiratory airway pressure (aOR per one cmH2O decrease, 1.05; 95% CI 1.00-1.09) remained significantly associated with extubation failure. In our study, being underweight and lower maximal inspiratory airway pressure was associated with post-extubation respiratory failure after a planned extubation.