Background: Prophylaxis with posaconazole (PP) has shown to be effective in the prevention of invasive fungal infections in immunocompromised adult patients. However, evaluation of its effectiveness and safety in children is limited. The aim of the study was to describe the use of posaconazole as antifungal prophylaxis in children. Methods: We reviewed the medical records of immunocompromised patients under 13 years of age with hematological diseases and post hematopoietic stem cell transplantation (HSCT) who received antifungal PP at the Instituto Nacional de Salud del Niño San Borja (Perú) from January 2014 to December 2018. Results: Fifty-six antifungal prophylaxis events were identified in 47 patients with a median age of 7.5 years (interquartile range [IQR] 4-10), 51.6% (n=24) of whom were female. The main underlying medical conditions were aplastic anemia (n=19, 33.9%), acute lymphoblastic leukemia (n=18, 32.1%), acute myeloid leukemia (n=14, 25.0%), and 34.1% had undergone HSCT. The median dose of posaconazole was 13.62 mg/kg/day (IQR: 12.0-16.8), and the median duration of PP was 24 days (IQR: 16-82). Gastrointestinal symptoms included abdominal pain (17.9%), nausea (16.1%), diarrhea (7.1%) and vomiting (3.6%). Elevated alanine aminotransferase and aspartate aminotransferase levels were observed in 9/35 patients (25.7%) and 10/51 (19.6%) patients, respectively. Five cases of breakthrough fungal infection were identified (8.9%). Conclusions: Breakthrough fungal infection, increased transaminase levels and gastrointestinal symptoms were observed during PP in children under 13 years of age.