Inhalation injury (INH) is present in one third of large burn injuries and increases oxygenation and fluid resuscitation requirements, incidences of pulmonary complications, risk for multiple organ dysfunction syndrome (MODS), and overall mortality. Previous studies have demonstrated inconsistent correlation between bronchoscopic evaluation and clinical outcomes. The authors reviewed 161 patients admitted with a diagnosis of INH or underwent diagnostic bronchoscopy for suspected INH over a period of 8.5 years. One hundred one patients had concomitant burn injury and 60 had isolated INH. Seventeen patients had abbreviated injury score (AIS) 0, 81 patients had low-grade injury (AIS 1 and 2), and 63 patients had high-grade injury (AIS 3 and 4). Patients with high-grade INH had worse pulmonary dysfunction, worse oxygenation indices (P = 0.01) and plasma carboxyhemoglobin (COHgb; P < 0.01) on admission, increased fluid requirements (P < 0.01 at 24 hours; P = 0.04 at 48 hours), MODS (P = 0.04), pneumonia (P < 0.01), acute respiratory distress syndrome (P = 0.01 at 48 hours), fewer 28-day ventilator-free days (P < 0.01), greater ventilator dependence (P = 0.03), and longer length of stay (P < 0.01). Multivariate analyses demonstrated increased risk of MODS (P = 0.03), acute respiratory distress syndrome at 48 hours (P < 0.01), pneumonia (P = 0.01), prolonged ventilator dependence (P = 0.03), and a trend toward mortality (P = 0.08) with higher AIS groups. More severe INH correlates with early oxygenation impairments and is associated with more complicated hospitalization, fluid resuscitation requirements, and ventilation demands. Severe INH is associated with and predictive of increased morbidity and mortality.