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Background: Hand, foot, and mouth disease (HFMD) mostly affects the health of infants and preschool children. Many studies of HFMD in different regions have been published. However, the epidemiological characteristics and space-time patterns of individual-level HFMD cases in a major city such as Beijing are unknown. The objective of this study was to investigate epidemiological features and identify high relative risk space-time HFMD clusters at a fine spatial scale. Methods: Detailed information on age, occupation, pathogen and gender was used to analyze the epidemiological features of HFMD epidemics. Data on individual-level HFMD cases were examined using Local Indicators of Spatial Association (LISA) analysis to identify the spatial autocorrelation of HFMD incidence. Spatial filtering combined with scan statistics methods were used to detect HFMD clusters. Results: A total of 157,707 HFMD cases (60.25% were male, 39.75% were female) reported in Beijing from 2008 to 2012 included 1465 severe cases and 33 fatal cases. The annual average incidence rate was 164.3 per 100,000 (ranged from 104.2 in 2008 to 231.5 in 2010). Male incidence was higher than female incidence for the 0 to 14-year age group, and 93.88% were nursery children or lived at home. Areas at a higher relative risk were mainly located in the urban-rural transition zones (the percentage of the population at risk ranged from 33.89% in 2011 to 39.58% in 2012) showing High-High positive spatial association for HFMD incidence. The most likely space-time cluster was located in the mid-east part of the Fangshan district, southwest of Beijing. Conclusions: The spatial-time patterns of Beijing HFMD (2008–2012) showed relatively steady. The population at risk were mainly distributed in the urban-rural transition zones. Epidemiological features of Beijing HFMD were generally consistent with the previous research. The findings generated computational insights useful for disease surveillance, risk assessment and early warning. [ABSTRACT FROM AUTHOR]