ObjectiveTo systematically review the association between acid suppressive drug use and fracture risk in children and adolescents. MethodsThe PubMed, Web of Science, EMbase, Cochrane Library, CNKI and WanFang Data databases were electronically searched to collect observational studies on the association between acid suppressive drug use and fracture risk in children and adolescents from inception to October 1, 2022. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using R4.1.2 software. ResultsA total of 6 studies involving 1 886 423 children and adolescents were included. Meta-analysis results showed that the use of proton pump inhibitors (PPIs) increased the risk of fracture (RR=1.19, 95%CI 1.10 to 1.29, P<0.01), whereas the use of histamine H2 receptor antagonists (H2RAs) did not increase the risk of fracture (P>0.05). Subgroup analysis showed that PPIs use increased risk of fracture in the lower limb and other sites (P<0.05). ConclusionCurrent evidence shows that PPIs can increase fracture risk in children and adolescents, but no association has been found between the use of H2RAs and increased fracture risk in this group. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.