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The aim of the study was to describe our experience with bi-level positive airway pressure (BiPAP) ventilation in oncology children with acute respiratory failure, hospitalized in a single tertiary pediatric tertiary center. This was a retrospective cohort study of all pediatric oncology patients in our center admitted to the intensive care unit with acute hypoxemic or hypercarbic respiratory failure from January 1999 through May 2006, who required mechanical ventilation with BiPAP. Fourteen patients met the inclusion criteria with a total of 16 events of respiratory failure or impending failure: 12 events were hypoxemic, 1 was combined hypercarbic and hypoxemic, and 3 had severe respiratory distress. Shortly after BiPAP ventilation initiation, there was a statistically significant improvement in the respiratory rate (40.4 ± 9.3 to 32.5 ± 10.1, P < .05] and a trend toward improvement in arterial partial pressure of oxygen (Pao2; 71.3 ± 32.7 to 104.6 ± 45.6, P = .055). The improvement in the respiratory status was sustained for at least 12 hours. In 12 (75%) events there was a need for sedation during ventilation; 12 children needed inotropic support during the BiPAP ventilation. Bi-level positive airway pressure ventilation failed in 3 (21%) children who were switched to conventional ventilation. All of them have died during the following days. One child was recategorized to receive palliative care while on BiPAP ventilator and was not intubated. In 12 of 16 BiPAP interventions (75%; 11 patients), the children survived to pediatric intensive care unit (PICU) discharge without invasive ventilation. No major complications were noted during BiPAP ventilation. Bi-level positive airway pressure ventilation is well tolerated in pediatric oncology patients suffering from acute respiratory failure and may offer noninferior outcomes compared with those previously described for conventional invasive ventilation. It appears to be a feasible initial option in children with malignancy experiencing acute respiratory failure.