Abstract: Objective To analyze epidemiological characteristics of hand-foot-mouth disease (HFMD) in Nanjing, and to explore the temporal and spatial clustering, in order to provide decision making strategy for control and prevention of severe HFMD. Methods Descriptive epidemiologic methods were used to analyze severe HFMD data in Nanjing during 2009-2016 from the Chinese Disease Surveillance Information Reporting System. Time-space rescheduling scanning analysis was used to explore spatial characteristics. Results A total of 1 526 severe HFMD cases were reported in Nanjing from 2009 to 2016, the annual average cases was 191(93 to 284). The proportion of severe HFMD was 11‰ (6‰-20‰) and there was no significant change in the tendency (Z=-1.5, P=0.125). The reported incidence rate for population ≤ 5 years old was 53/100 000 (21/100 000 to 76/100 000). The peak time was April to July (54%) in each year. The proportion of male cases was 64%. The median age was 2 (0-13) years. The proportion of cases aged under 5 years was 97%, in which cases aged 1-3 years was 75%. The proportion for scattered children was 67% and for preschool children was 31%. The temporal and spatial clustering existed among severe HFMD cases between 2009 and 2016 except for 2013, which was shifting to the south of the city, including Jiangning, Yuhuatai and Lishui, from the centre. The temporal dimension of severe HFMD was from March to July in each year (all P<0.001). The positive rate of Enterovirus for severe HFMD cases was 39% (17%~70%). The proportion of EV71 and CoXA16 were 75% (54%-89%) and 5% (0-17%), respectively. Conclusions Epidemiological characteristics of severe HFMD cases were consistent with common cases in Nanjing. EV71 was the main pathogen which caused the severe cases. Monitoring among high risk areas and populations and the EV71 vaccination are essential measures.