Inhaled heparin/N-acetylcystine (AHA) has been reported to decrease mortality in children with inhalation injury. The use of AHA therapy in adult burn patients with inhalation injury has not been evaluated. We hypothesized that patients who received AHA therapy in the management of inhalation injury would have better pulmonary mechanics and better clinical outcomes than patients who did not. This study is a retrospective chart review of pulmonary mechanics and clinical outcomes in all inpatients identified in the institutional ABA/TRACS database as having sustained inhalation injury from 1999 to 2005. Patients were not assigned to a treatment group. One hundred and fifty patients with inhalation injury were identified. Sixty-two patients were treated with AHA during the first 72 hours of admission. Treatment occurred mostly in patients admitted after 2002, with only 18 patients receiving AHA from 1999 through 2002. Treated and untreated patients did not differ in age or TBSA burn injury, nor did any studied clinical outcome differ between treated and untreated groups. In addition, there was no difference in pulmonary findings at 1 week after injury between treated and untreated patients. Although best Pao2 was higher in treated patients during the first 72 hours, this was not a durable finding, and the best Pao2/Fio2 ratio was unaffected by treatment. Importantly, the use of AHA in adults with inhalation injury did not affect clinical outcomes. A prospective, randomized trial would be of benefit to delineate the clinical benefits of AHA treatment for inhalation injury.