Acute bacterial lymphadenitis is a common childhood condition, yet there remains considerable variability in antibiotic treatment choice, particularly in settings with low prevalence of methicillin-resistantStaphylococcus aureussuch as Europe and Australasia. This retrospective cross-sectional study reviewed children presenting with acute bacterial lymphadenitis to a tertiary paediatric hospital in Australia between 1 October 2018 and 30 September 2020. Treatment approaches were analysed with respect to children with complicated versus uncomplicated disease. A total of 148 children were included in the study, encompassing 25 patients with complicated disease and 123 with uncomplicated lymphadenitis, as defined by the presence or absence of an associated abscess or collection. In culture-positive cases, methicillin-susceptibleS. aureus(49%) and Group A Streptococcus (43%) predominated, while methicillin-resistantS. aureuswas seen in a minority of cases (6%). Children with complicated disease generally presented later and had a prolonged length of stay, longer durations of antibiotics, and higher frequency of surgical intervention. Beta-lactam therapy (predominantly flucloxacillin or first-generation cephalosporins) formed the mainstay of therapy for uncomplicated disease, while treatment of complicated disease was more variable with higher rates of clindamycin use.Conclusion: Uncomplicated lymphadenitis can be managed with narrow-spectrum beta-lactam therapy (such as flucloxacillin) with low rates of relapse or complications. In complicated disease, early imaging, prompt surgical intervention, and infectious diseases consultation are recommended to guide antibiotic therapy. Prospective randomised trials are needed to guide optimal antibiotic choice and duration in children presenting with acute bacterial lymphadenitis, particularly in association with abscess formation, and to promote uniformity in treatment approaches.What is Known:• Acute bacterial lymphadenitis is a common childhood infection.• Antibiotic prescribing practices are highly variable in bacterial lymphadenitis.What is New:• Uncomplicated bacterial lymphadenitis in children can be managed with single agent narrow-spectrum beta-lactam therapy in low-MRSA prevalence settings.• Further trials are needed to ascertain optimal treatment duration and the role of clindamycin in complicated disease.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00431-023-04861-0.