Abstract: Objective To explore the multiple infection status of hand, foot and mouth disease (HFMD) and its epidemiological characteristics in Hefei City to provide scientific evidence for HFMD prevention and control. Methods The cases of multiple infection of HFMD living in Hefei were screened out from National Notifiable Disease Report System and analyzed by descriptive epidemiology. Results The incidence of reinfection of HFMD in Hefei from 2011 to 2016 was 10.73 per 100 000, and the incidence of multiple infections was 5.12%. 83.36% of the reinfection occurred within two years of the last infection. The median age of first infection among multiple infections was 1.94 years old and single infection cases was 2.30 years old, there was significant difference (Z=-28.84,P<0.001). The incidence of multiple infections in the 0-year-old group was the highest (8.15%), and the incidence of multiple infections decreased with age in children less than 6 years old (χ_trend²=609.28, P<0.001). Boys were more susceptible to multiple infections, and reinfection cases were mainly occurred by the children in kindergarten. The incidence of reinfection was also high in areas with high incidence of HFMD. Conclusions Multiple infections of HFMD is a serious common health threat to children in Hefei. We should pay more attention to the population including boys with a first onset age less than three years old, kindergarten children as well as children from areas with high incidence and take prevention and control measures.