BACKGROUND: Antibiotics are overprescribed for children with upper respiratory infections (URIs), leading to unnecessary expenditures, adverse events and antibiotic resistance. This study assesses whether interventions antibiotic prescription rates (APR) for childhood URIs can be reduced and what factors impact intervention effectiveness. METHODS: MEDLINE, Embase, Google Scholar, Web of Science, Global Health, WHO website, United States CDC website and The Cochrane Central Register of Controlled Trials (CENTRAL) were searched by December 2015. Cluster or individual-patient randomised controlled trials (RCTs) and non-RCTs that examined interventions to change APR for children with URIs were selected for meta-analysis. Educational interventions for clinicians and/or parents were compared with usual care. RESULTS: Of 6074 studies identified, 13 were included. All were conducted in high-income countries. Interventions were associated with lower APR versus usual care (OR 0.63 (95% CI 0.50 to 0.81, p<0.001). A patient-clinician communication approach was the most effective type of intervention, with a pooled OR 0.41 (95% CI 0.20 to 0.83; p<0.001) for clinicians and 0.26 (95% CI 0.08 to 0.91; p=0.04) for parents. Interventions that targeted clinicians and parents were significant, with a pooled OR of 0.52 (95% CI 0.35 to 0.78; p=0.002). Insignificant effects were observed for targeting clinicians and parents alone, with a pooled OR of 0.88 (95% CI 0.67 to 1.16; p=0.37) and 0.50 (95% CI 0.10 to 2.51, p=0.40), respectively. CONCLUSIONS: Educational interventions are effective in reducing antibiotic prescribing for childhood URIs. Interventions targeting clinicians and parents are more effective than those for either group alone. The most effective interventions address patient-clinician communication. Studies in low-income to middle-income countries are needed.