Background: Invasive mould infections are a significant cause of morbidity and mortality in pediatric cancer patients, particularly in those undergoing aggressive myeloablative chemotherapy. Voriconazole has been described as an appropriate and effective prophylactic agent in adults with cancer. Methods: We compared the etiology, predisposing factors and outcomes of invasive mould infection in patients treated for acute myeloid leukemia before and after implementation of voriconazole prophylaxis in a pediatric cancer center. Results: We observed no difference in the number of invasive mould infection between groups. However, isolated organisms were markedly different, with a shift from aspergillosis to phaeohyphomycosis after the implementation of voriconazole prophylaxis. Survival at 90 days was improved in patients receiving voriconazole prophylaxis (P = 0.05). We did not identify a significant increase in the incidence of zygomycosis associated with routine use of voriconazole prophylaxis. Conclusions: Voriconazole prophylaxis was associated with improved survival in pediatric patients with acute myeloid leukemia, although other factors may be involved. Voriconazole prophylaxis was associated with a marked change in the pattern of mould infections, with a significant reduction in aspergillosis