BackgroundHand, foot, and mouth disease (HFMD) is a public health issue in Hubei and studies of- spatiotemporal clustering at a fine scale are limited. The purpose of this research was to analyze the epidemiological characteristics, temporal variation characteristics, and spatiotemporal clustering of HFMD cases at the town level from 2009 to 2019 to improve public health outcomes.MethodsMathematical statistics, a seasonal index, wavelet analysis, and spatiotemporal scans were used to analyze epidemiological characteristics, time series trends, and spatiotemporal clusters of HFMD in Hubei.ResultsEV-A71 (Enterovirus A71) and CVA16 (Coxsackievirus A16) constitute the two primary pathogens of the HFMD epidemic in Hubei, among which EV-A71 is the dominant pathogen, especially in 2016. In terms of age distribution, a major peak occurred at 0–5 years and a very small increase appeared at 25–35 years, with the former having a higher incidence among males than females and the latter having the opposite difference between males and females. The number/rate of HFMD cases exhibited a considerable increase followed by a moderate decline from 2009 to 2019, with the first large peak in April-July and a smaller peak in November-December. HFMD in Hubei exhibited the characteristics of a 270-day cycle with multiscale nesting, which was similar to the periodicity of HFMD cases caused by EV-A71 (9 months). Cities with a higher incidence of HFMD formed a part of an “A-shaped urban skeleton”. Subdistricts had the highest incidence of HFMD, followed by towns and villages. The spatiotemporal scan results showed one most likely cluster and 22 secondary clusters, which was consistent with the geographic location of railways and rivers in Hubei.ConclusionsThese findings may be helpful in the prevention and control of HFMD transmission and in implementing effective measures in Hubei Province.