Death and the incidence of pneumonia are significantly increased in burn patients with inhalation injury, despite application of conventional ventilatory support techniques. The effect of high-frequency percussive ventilation on mortality rate, incidence of pulmonary infection, and barotrauma were studied in 54 burn patients with documented inhalation injury admitted between March 1987 and September 1990 as compared to an historic cohort treated between 1980 and 1984. All patients satisfied clinical criteria for mechanical ventilation. High-frequency percussive ventilation was initiated within 24 hours of intubation. The patients' mean age and burn size were 32.2 years and 47.8%, respectively (ranges, 15 to 88 years; 0% to 90%). The mean number of ventilator days was 15.3 ± 16.7 (range, 1 to 150 days), with 26% of patients ventilated for more than 2 weeks. Fourteen patients (25.9%) developed pneumonia compared to an historic frequency of 45.8% (p < 0.005). Mortality rate was 18.5% (10 patients) with an expected historic number of deaths of 23 (95% confidence limits of 17 to 28 deaths). The documented improvement in survival rate and decrease in the incidence of pneumonia in patients treated with prophylactic high-frequency ventilation (HFV), as compared to a cohort of patients treated in the 7 years before the trial, indicates the importance of small airway patency in the pathogenesis of inhalation injury sequelae and supports further use and evaluation of HFV.