Objective of this study The mortality level of leucemic patient's fungal infections can reach 70 %. Antifungal prophylaxis posaconazole (P) is used during severe and prolonged neutropenia resulting from chemotherapy for acute myelogenous leukemia (AML), myelodysplastic syndrome and after autologous transplant. Patients and methods We realized a retrospective study in order to assess the efficiency of P. Oral prophylaxy dosage is 200 mg every eight hours to beginning before presumed neutropenia. Treatment failure was defined as the occurrence of proven/probable invasive fungal infections (IFI), receipt of any other systemic antifungal agent for suspected IFI or for impossible swallowing and the occurrence of adverse event. The objective is to note down the incidence of proven/probable IFI prevented by P. Results We included 22 patients of whom 86 % suffered from AML. P was prescribed in IFI prophylaxies during prolonged and severe neutropenia postchemotherapy (72 %) or postautologous transplant (28 %) and initiated 7 days before neutropenia (50 % of cases). The mean treatment period was 18 days. Colonization occurred in one third of patients (43 % of Candida albicans) . Esomeprazole (E) 40 mg was associated in 64 % of cases. P prophylaxis failed in 50 % of cases. Proven/probable IFI occurred in one case. Different failure causes were: suspected or possible IFI ( n = 5) and impossible swallowing ( n = 5). Conclusion P prophylaxis seems to be efficient among these high-risk patients. However, a P tardive initiation, an E association, P administration and resorption difficulties seem to have a importance in successful treatment. It would be interesting to optimize P treatment with plasmatic dosages to ensure efficiency and safety for patients.