Abstract: Objective To estimate the prevalence of recurrent infection of hand-foot-and-mouth disease (HFMD) by Metaanalysis.Methods By using Chinese Web of Knowledge,Wanfang,Weipu,PubMed,and Web of Science databases,a systematic literature search with keywords included ("repeated infection" OR recurred OR reoccurrence OR "multiple infection" OR "multiple infection" OR "reinfection" OR "reoccurring infection" OR "recurrent infection") AND ("HFMD" OR "hand-foot-and-mouth Disease") AND "rate" both in Chinese and English.The quality of each paper was evaluated with "critical appraisal of the health research literature:prevalence or incidence of a health problem".Random-effects Meta-analysis was used to estimate recurrent infection prevalence of HFMD by comprehensive Meta-analysis.Subgroup analyses were conducted by study years,study location,publication year,sample size,standard of repeated infection,repeated infection times,gratitude and average temperature per year to explore the heterogeneity.Egger test were performed to evaluate the publication bias.Sensitivity analysis was evaluated by iteratively removing one study at a time and comparing the recalculated combined estimates.Results Thirty-one studies were included in the analysis.The combined prevalence of recurrent infection of HFMD was 2.25% (95%CI=1.59%-3.18%).Cochran's Q test showed a high degree of heterogeneity across studies(I2=99.87,P =0.000).Subgroup analysis estimated that the heterogeneity had a certain distinction at the indexes of sample size,study years,standard of repeated infection,repeated infection times,gratitude and average temperature per year.Conclusion Significant regional differences in recurrent infection of HFMD are found across China.Further investigation should focus on the sources of heterogeneity.