Acute respiratory distress syndrome (ARDS) in children after open heart surgery, although uncommon, can be a significant source of morbidity. Because high-frequency oscillatory ventilation (HFOV) had been used successfully with pediatric patients who had no congenital heart defects, this therapy was used in our unit. This report aims to describe a single-center experience with HFOV in the management of ARDS after open heart surgery with respect to mortality. This retrospective clinical study was conducted in a pediatric intensive care unit. From October 2008 to August 2012, 64 of 10,843 patients with refractory ARDS who underwent corrective surgery at our institution were ventilated with HFOV. Patients with significant uncorrected residual lesions were not included. No interventions were performed. The patients were followed up until hospital discharge. The main outcome measure was survival to hospital discharge. Severe ARDS was defined as acute-onset pulmonary failure with bilateral pulmonary infiltrates and an oxygenation index (OI) higher than 13 despite maximal ventilator settings. The indication for HFOV was acute severe ARDS unresponsive to optimal conventional treatment. The variables recorded and subjected to multivariate analysis were patient demographics, underlying disease, clinical data, and ventilator parameters and their association with hospital mortality. Nearly 10,843 patients underwent surgery during the study period, and the ARDS incidence rate was 0.76 % (83/10,843), with 64 patients (77 %, 64/83) receiving HFOV. No significant changes in systemic or central venous pressure were associated with initiation and maintenance of HFOV. The complications during HFOV included pneumothorax for 22 patients. The overall in-hospital mortality rate was 39 % (25/64). Multiple regression analyses indicated that pulmonary hypertension and recurrent respiratory tract infections (RRTIs) before surgery were independent predictors of in-hospital mortality. The findings show that HFOV is an effective and safe method for ventilating severe ARDS patients after corrective cardiac surgery. Pulmonary hypertension and RRTIs before surgery were risk factors for in-hospital mortality.