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High frequency oscillatory ventilation (HFOV) has been successfully used in the management of acute respiratory distress syndrome (ARDS) in children. The aim of our study is to determine its effectiveness in pediatric patients with cancer or post hematopoietic stem cell transplantation (HSCT) diagnosed with ARDS.A retrospective case review, in a pediatric intensive care unit (PICU) in a tertiary-care oncology center in Amman, Jordan. Patients included were children with cancer and/or receiving allogeneic HSCT who were diagnosed with ARDS and placed on HFOV from January 2007 to February 2009.Data from 12 pediatric oncology patients on HFOV were analyzed for demographics, oncological diagnosis, PRISM III scores, ventilator settings before switching to HFOV and 24 hours after switching, complications, and outcomes. Alveolar–arterial oxygen (A–a) gradient and oxygen index (OI) were calculated, and pressure of arterial CO2 (PaCO2) was measured before and 24 hours after switching. Endpoints were successful extubation and discharge, or death while intubated. After 24 hours on HFOV, the A–a gradient decreased significantly in all patients (from a median of 564–267 torr; P = 0.001). OI decreased in all but two patients who died (median 17); PaCO2 decrease was not significant. Five patients died (two of them post-HSCT) and the 7 (58%) survivors were weaned from HFOV (median, 9 days) and discharged.HFOV improves gas exchange and is useful in managing critically ill children with cancer and post-HSCT patients who develop ARDS. Pediatr Blood Cancer 2012; 58: 384–389. © 2011 Wiley Periodicals, Inc.