Data about the effectiveness of high frequency oscillatory ventilation (HFOV) in children with respiratory failure are limited. This study investigated the efficacy and prognostic factors of this treatment. Methods: Children between 2 months and 18 years of age who received HFOV between January 2000 and September 2006 in a tertiary care center were enrolled in this retrospective study. Results: Thirty-six HFOV treatments were given to 33 patients (twice in one patient and three times in another patient) at a mean age of 5.4 ± 5.0 years. HFOV was used as a rescue after conventional mechanical ventilation (CMV) for 4.4 ± 4.2 days. The mean duration of HFOV was 7.6 ± 7.9 days. The most common indication for HFOV was oxygenation failure, which was due to pneumonia with acute respiratory distress syndrome in 15 (45.5%), severe lobar pneumonia in nine (27.3%), pulmonary hemorrhage in eight (24.2%) and pneumothorax in one (3%). PaCO2 was significantly improved 4 hours after HFOV and the PaO2/FiO2 ratio increased significantly 12 hours later. The oxygenation index and alveolar-arterial oxygen difference P(A-a)O2, however, did not change markedly. Four (12%) patients needed further extracorporeal life support and two of these survived. The overall survival rate was 45.5%. Patients with heavier body weight (p < 0.05) and of the male gender (p < 0.05) had a higher risk of mortality. Conclusion: As a relatively late rescue therapy after failure of CMV, HFOV may improve PaCO2 and PaO2/FiO2 in children with respiratory failure. However, it carries an increased mortality rate in patients with heavier body weight and male gender.