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Rationale: Subglottic edema is the most common cause of pediatric extubation failure, but few studies have confirmed risk factors or prevention strategies. This may be due to subjective assessment of stridor or inability to differentiate supraglottic from subglottic disease., Objectives: Objective 1 was to assess the utility of calibrated respiratory inductance plethysmography (RIP) and esophageal manometry to identify clinically significant post-extubation upper airway obstruction (UAO) and differentiate subglottic from supraglottic UAO. Objective 2 was to identify risk factors for subglottic UAO, stratified by cuffed versus uncuffed endotracheal tubes (ETTs)., Methods: We conducted a single-center prospective study of children receiving mechanical ventilation. UAO was defined by inspiratory flow limitation (measured by RIP and esophageal manometry) and classified as subglottic or supraglottic based on airway maneuver response. Clinicians performed simultaneous blinded clinical UAO assessment at the bedside., Measurements and Main Results: A total of 409 children were included, 98 of whom had post-extubation UAO and 49 (12%) of whom were subglottic. The reintubation rate was 34 (8.3%) of 409, with 14 (41%) of these 34 attributable to subglottic UAO. Five minutes after extubation, RIP and esophageal manometry better identified patients who subsequently received UAO treatment than clinical UAO assessment (P < 0.006). Risk factors independently associated with subglottic UAO included low cuff leak volume or high preextubation leak pressure, poor sedation, and preexisting UAO (P < 0.04) for cuffed ETTs; and age (range, 1 mo to 5 yr) for uncuffed ETTs (P < 0.04). For uncuffed ETTs, the presence or absence of preextubation leak was not associated with subglottic UAO., Conclusions: RIP and esophageal manometry can objectively identify subglottic UAO after extubation. Using this technique, preextubation leak pressures or cuff leak volumes predict subglottic UAO in children, but only if the ETT is cuffed.