We aimed to provide real-life information about the effectivity of different types of primary antifungal prophylaxis (AFP) in patients with acute myeloid leukemia (AML). Records of AML patients who received remission-induction chemotherapy between June 2010 and February 2013 were retrospectively reviewed. A total of 85 AML remission-induction chemotherapy cycles were identified in 80 patients. Fluconazole prophylaxis (FP) was administered in 29 cycles, and posaconazole prophylaxis was given in 56 cycles. Failure in the AFP was observed in 45 (57.9 %) out of 85 cycles. Any type of invasive fungal diseases were detected in 15 (26.8 %) out of 56 cycles receiving posaconazole and 15 (51.7 %) out of 29 cycles receiving fluconazole (p = 0.023). Relapsing or refractory AML, longer duration of neutropenia and FP were more common in patients with AFP failure. Multivariate logistic regression analysis showed that type of AFP (odds ratio (OR) 3.63; 95 % confidence interval (CI) 1.19-11.07), presence of neutropenia longer than 21 days (OR 3.96; 95 % CI 1.36-11.46), and refractory or relapsing AML (OR 6.09; 95 % CI 2.09-17.73) were independent factors associated with failure of AFP. We observed superiority of posaconazole on fluconazole in the prophylaxis of AML patients receiving remission-induction chemotherapy.