Objective To analyze the epidemic characteristics of the hand-foot-mouth disease (HFMD) in four years before and after EV71 vaccine inoculation, and to provide a basis for better EV71 vaccination and prevention and control of HFMD. Methods The descriptive epidemiology method was used to analyze the monitoring data of HFMD from 2013 to 2020 and EV71 vaccination from 2017 to 2020 in Xinwu District of Wuxi City. Results A total of 9 589 HFMD cases including 104 severe cases (accounting for 1.08%) were reported in four years before EV71 vaccination, and the reported average annual incidence rate was 431.15/100 000. A total of 7 396 HFMD cases including 21 severe cases (accounting for 0.28%) were reported in four years after vaccine inoculation, and the reported average annual incidence rate was 325.28/100,000. Annual incidence rate and severe illness rate decreased significantly before and after vaccine inoculation. The HFMD incidences displayed two epidemic peaks, from May to June and from October to November. The three streets with the highest average annual incidence were Jiangxi, Meicun, and Shuofang. The HFMD cases were mainly children under 5 years old, and there were more men than women. A total of 394 samples were sent for examination from 2013-2020, and 231 were positive, with a total positive rate of 58.63%. There were significant changes in the etiological composition before and after vaccine inoculation. The composition of EV71 virus decreased significantly (χ²=69.70, P<0.05), while CA16 and CA6 increased significantly (χ²=22.35, P<0. 05). From 2017 to 2020, a total of 12 472 people were inoculated with EV71 vaccine in Xinwu District of Wuxi City, with estimated annual vaccination rates of 3.78%, 10.96%, 8.40% and 7.63%, respectively. Conclusion There is no significant change in time, region and population distribution of HFMD before and after EV71 vaccination in Xinwu District of Wuxi City, but the annual incidence rate and severe illness rate show a decreasing trend, and the dominant intestinal pathogens have changed. It is suggested to strengthen the use of EV71 vaccine and the development of multivalent HFMD-related vaccine.