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Febrile neutropenia (FN) is a frequent, serious complication of intensive pediatric chemotherapy regimens. The aim of this trial was to compare quality of life (QOL) between inpatient and outpatient intravenous antibiotic management of children and adolescents with low risk febrile neutropenia (LRFN).In this randomised non-blinded trial, patients between 1 and 21 years old, receiving low/moderate intensity chemotherapy were pre-consented and, on presentation to emergency (ED) with FN satisfying low risk criteria, randomised to either outpatient or inpatient care with intravenous cefepime 50 mg/kg (12 hourly). All patients continued antibiotics for at least 48 hours, until afebrile for 24 hours and demonstrating a rising absolute neutrophil count ≥200/mm3. Several domains of QOL were examined by daily questionnaire.Eighty-one patients presented to ED with 159 episodes of fever. Thirty-seven FN presentations involving 27 patients were randomised to inpatient (18) and outpatient (19) management. Combined QOL mean scores for parents were higher for the outpatient group and scores for three specific parent variables (keeping up with household tasks/time spent with partner/time spent with other children) were higher among outpatients. There was no difference in parent confidence/satisfaction in care between groups. Patients scored better in the outpatient group overall and for sleep and appetite. The mean length of fever was equivalent between groups and there were no serious adverse events attributable to cefepime or outpatient care.Outpatient cefepime management of LRFN provided significant benefit to parents and patients across several QOL domains and appeared both feasible and safe. Pediatr Blood Cancer 2014; 61:1427–1433. © 2014 Wiley Periodicals, Inc.