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Hand, foot, and mouth disease (HFMD) is a common childhood illness that is caused by enteroviruses, and the prevalence of HFMD in China and around the world has resulted in a huge disease burden. Since 2010, the HFMD incidence has been the highest among infectious diseases in Suzhou, China. To investigate the epidemical, features, etiological characteristics, and clinical characteristics of HFMD in Suzhou City, East China, from 2011 to 2014. We retrospectively analyzed HFMD epidemiological data in Suzhou from 2011 to 2014. A total of 80,723 outpatients in the city of Suzhou were diagnosed with HFMD, including 1,846 severe cases. There were 2,387 (3.0 %) laboratory-confirmed cases, 807 of which exhibited severe symptoms. All analyses were stratified by age, disease severity, laboratory confirmation status, and enterovirus subtype. From 2011 to 2014, HFMD mainly affected children aged 1-3, and boys were more affected than girls. The highest peak incidences of HFMD occurred in May or June from 2011 to 2014, and lower peak incidences were observed from November to December and in districts with higher humidity. Enterovirus 71 and coxsackievirus A16 were the predominant viral genotypes in Suzhou in 2011 to 2012 and 2014, and the severe cases mainly correlated with EV71 subtypes. In 2013, other EVs were dominant. The proportion of patients with severe disease decreased significantly, and the VP1 capsid proteins of EV71 and CA16 from severe and mild cases were nearly identical. This study shows that it is time to start monitoring EVs in China and that we should accelerate vaccine research and develop public-health interventions for the control and prevention of HFMD, all of which will play an important role in the prevention of HFMD. [ABSTRACT FROM AUTHOR]