We retrospectively analyzed the efficacy of non-invasive ventilation in 35 patients with acute hypoxemic respiratory failure after autologous or allogeneic stem cell transplantation (SCT). Non-invasive ventilation was delivered by a standard face mask or helmet. Decisions to intubate were made according to standard criteria. Between 1993 and 2003, 836 patients underwent an autologous or allogeneic bone marrow or SCT. Eighty-two patients developed respiratory failure. Of these, 47 patients were initially intubated and mechanically ventilated. None of these patients survived. Thirty-five patients initially underwent non-invasive ventilation at the bone marrow transplant unit. Seven of these patients survived and were discharged from the hospital (20%). Eleven of the 35 (31%) patients improved within the first 4 h of non-invasive ventilation with respect to oxygenation and were regarded as responders. Seven of these patients survived to hospital discharge (64%), while all non-responders died (P<0.001). In all survivors, the partial pressure of arterial oxygen (PaO2) improved after the initiation of non-invasive ventilation. In non-survivors, PaO2 improved in only 4 of 28 patients (17%) (P<0.0001). Non-invasive ventilation in patients with acute respiratory failure after SCT could improve prognosis in a carefully selected group of patients.