ObjectivesAcute otitis media (AOM) is a common childhood infection. Recurrent AOM affects a subset of children, resulting in an adverse impact on quality of life, socioeconomic disadvantage, and risk of long‐term sequelae. Antimicrobial chemoprophylaxis is used in some settings but is increasingly controversial due to an awareness of adverse long‐term effects and contribution to global antibiotic resistance.Design and SettingA comprehensive literature search was undertaken using Medline (1946–October 2023) and Embase (1974–October 2023). The primary aim was to assess the efficacy of antimicrobial chemoprophylaxis on AOM episodes in children < 18 years of age. Bias and quality assessment was performed. Dichotomous data were analysed using risk ratio with 95% confidence intervals. Meta‐analysis was carried out using random‐effects models for pooled analysis, independent of heterogeneity. Heterogeneity was assessed using the I2 statistic.Main Outcome MeasuresThe effect of antimicrobial chemoprophylaxis in children with rAOM on the number of individual AOM episodes. Secondary outcomes: assessment of antimicrobial agents and outcomes in children with risk factors.ResultsAssessment of qualitative data was performed on 20 studies (n = 2210). No controlled trials were identified post‐multivalent pneumococcal conjugate vaccine (PCV) introduction, restricting current generalisability. Quantitative meta‐analysis on nine pre‐PCV studies (n = 1087) demonstrated antimicrobial chemoprophylaxis reduced any episode of AOM with a risk ratio 0.59 (95% CI 0.45–0.77).ConclusionFamilies and clinicians must balance marginal short‐medium term benefit (based on pre‐PCV data), and the potential for adverse effects to that individual, and the societal risk of antimicrobial resistance with prolonged antibiotic use.