BACKGROUND: Re-intubation is associated with high morbidity and mortality. There is limited information regarding the risk factors that predispose patients admitted to the surgical ICU to re-intubation. We hypothesized that preoperative comorbidities, acquired muscular weakness, and renal dysfunction would be predictors of re-intubation in the surgical ICU population. METHODS: This was a prospective observational study in 2 surgical ICUs of a large tertiary hospital. All patients who were extubated during their surgical ICU stay were included. Demographic and clinical data were collected before and after extubation. The primary outcome was re-intubation within 72 h. Using multivariate logistic regression analysis, independent risk factors of re-intubation were determined, and a prediction score was developed. RESULTS: Between December 1, 2012, and January 31, 2014, we included 764 consecutive subjects. Of these, 65 subjects (8.5%) required re-intubation. Independent risk factors of re-intubation were blood urea nitrogen level of >8.2 mmol/L (odds ratio [OR] 3.66, 95% CI 1.97-6.80), hemoglobin level of <75 g/L (OR 2.10, 95% CI 1.23-3.61), and muscle strength of <3 (OR 2.03, 95% CI 1.16 -3.55). The presence of all 3 risk factors was associated with an estimated probability for re-intubation of 26.8%. CONCLUSIONS: In noncardiac surgery, surgical ICU subjects, elevated blood urea nitrogen level, low hemoglobin level, and muscle weakness were identified as independent risk factors for re-intubation. The presence of these risk factors can potentially aid clinicians in making informed decisions regarding optimal airway management in patients considered for an extubation attempt. (ClinicalTrials.gov registration NCT01967056.)