Introduction: While fever is the main complaint among pediatric emergency services and high antibiotic prescription are observed, only a few studies have been published addressing this subject. Therefore this systematic review aims to summarize antibiotic prescriptions in febrile children at the ED and assess its determinants. Methods: We extracted studies published from 2000 to 2017 on antibiotic use in febrile children at the ED from different databases. Author, year, and country of publishing, study design, inclusion criteria, primary outcome, age, and number of children included in the study was extracted. To compare the risk-of-bias all articles were assessed using the MINORS criteria. For the final quality assessment we additionally used the sample size and the primary outcome. Results: We included 26 studies reporting on antibiotic prescription and 28 intervention studies on the effect on antibiotic prescription. In all 54 studies antibiotic prescriptions in the ED varied from 15 to 90.5%, pending on study populations and diagnosis. Respiratory tract infections were mostly studied. Pediatric emergency physicians prescribed significantly less antibiotics then general emergency physicians. Most frequent reported interventions to reduce antibiotics are delayed antibiotic prescription in acute otitis media, viral testing and guidelines. Conclusion: Evidence on antibiotic prescriptions in children with fever presenting to the ED remains inconclusive. Delayed antibiotic prescription in acute otitis media and guidelines for fever and respiratory infections can effectively reduce antibiotic prescription in the ED. The large heterogeneity of type of studies and included populations limits strict conclusions, such a gap in knowledge on the determining factors that influence antibiotic prescription in febrile children presenting to the ED remains.