OBJECTIVE Prophylaxis with posaconazole (PP) is 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 younger than 13 years with hematologic diseases and post hematopoietic stem cell transplant (HSCT) who received antifungal PP at the Instituto Nacional de Salud del Niño San Borja (INSN-SB) in Lima, Peru, from January 2014 to December 2018. RESULTS Fifty-six courses of PP were identified in 47 patients with a median age of 7.5 years (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 Patients younger than 13 years who received PP showed an increase in transaminase values, and the development of breakthrough fungal infections. ABBREVIATIONS ALT, alanine aminotransferase; AST, aspartate aminotransferase; EORTC/MSG, European Organization for Research and Treatment of Cancer and Mycoses Study Group of the National Institute of Allergy and Infectious Diseases; FDA, US Food and Drug Administration; GvHD, graft-versus-host disease; HSCT, hematopoietic stem cell transplant; IFI, invasive fungal infection; INSN-SB, Instituto Nacional de Salud del Niño San Borja; PP, prophylaxis with posaconazole; PPI, proton pump inhibitor; TDM, therapeutic drug monitoring.