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Efficacy of posaconazole for prophylaxis was evaluated in 77 chemotherapy cycles in 59 patients with acute myeloid leukemia (AML) aged 39 (17–62) years from 2012 till 2017. Posaconazole was given in oral suspension 200 mg three times a day after meal during chemotherapy cycle or on 1st day after the cycle. Administration of posaconazole predominated in patients with de novo AML (84.5%) on 1st induction cycles (66.3%). Neutropenia was present in all patients with median duration of 22 days. Median duration of prophylaxis was 21 (2–57) days. Posaconazole prophylaxis was interrupted in 28 (36.4%) of 77 cases, mainly due to diarrhea (28.6%). In 17 (61%) of 28 cases prophylaxis was resumed within a median of 3 days. In 72 (93.5%) of cases duration of posaconazole prophylaxis was ≥ 7 days, in 5 (6.5%) cases < 7 days. Efficacy of prophylaxis was evaluated in cases of posaconazole duration ≥ 7 days. Invasive pulmonary aspergillosis (probable) was in 2 (2.7%) of 72 cases. Administration of posaconazole with duration ≥ 7 days was in 46 cases on chemotherapy cycle, in 26 cases – on first day after the cycle. Patients using Posaconazole after a course of chemotherapy in comparison with patients receiving the drug in the first days of the course had significantly less interruptions of prophylaxis (11,5% vs 41,3%, p=0.009) and a reduction in duration of Posaconazole using (19 days vs 27 days, p=0.007).One case of invasive aspergillosis was registered in each group.We confirmed the efficacy of posaconazole for prophylaxis of invasive mycoses in patients with AML. Administration of posaconazole prophylaxis on first day after the end of chemotherapy cycle results in saving of drug by reducing duration of posaconazole using by 8 days and does not increase the incidence of invasive mycoses.