Hand, foot and mouth disease (HFMD) is an acute contagious condition caused by a spectrum of human enteroviruses. HFMD reinfection is common in the absence of cross-protection from other virus subtypes. This study focused on reinfection in children in Anhui province, China between 2008 and 2013 using surveillance system data. We classified 8960 cases as reinfected, corresponding to a rate of 2·02%. The reinfection rate was higher in boys than in girls [odds ratio (OR) 1·27, 95% confidence interval (CI) 1·21–1·32, P < 0·001], children aged < 3 years (OR 3·82, 95% CI 3·58–4·07, P < 0·001), and children living in rural areas (OR 1·09, 95% CI 1·04–1·14, P = 0·001). The reinfection rate in children who were originally infected with non-enterovirus A71 (non-EVA71) enteroviruses was higher than those infected with EVA71 (OR 1·36, 95% CI 1·02–1·80, P = 0·034). Influential factors of reinfection rate included annual incidence (β coefficient = 0·715, P = 0·002) and the proportion of EVA71 in patients with mild HFMD (β coefficient = −0·509, P = 0·018). These results demonstrate that boys aged <3 years, especially those in rural areas or regions with a lower EVA71 proportion are more prone to reinfection, and specific health education programmes should be developed to protect these susceptible populations.