Objective To describe the epidemiological and etiological characteristics of hand, foot and mouth disease (HFMD) among children aged 5 years and younger in Ningbo after the access of entero-virus-A71 vaccine (2016 to 2019). Methods A retrospective cohort study were performed in children aged 5 years and younger in Ningbo from 2016 to 2019. Data for incidence of HFMD was collected from the National Notifiable Disease Surveillance Reporting System and the Electronic Medical Records (EMRs) System, while the demographic information was derived from the Immunization Information System. Speci-mens were detected by real-time fluorescence quantitative PCR and the Wilson method was used to estimate the incidence rate and 95% confidence interval. Results From 2016 to 2019, a total of 1 044 800 residential children were observed in this population-based cohort. In the study, 102 471 cases of HFMD were diagnosed in 2 651 081 person-years, revealing an overall incidence density of 3 865.25/100 000 person-years. There was no significant decline in the number of the cases after the vaccine was available. The number of the patients of hand foot mouth disease during the four years was 93 421, of whom 84 875 (90.85%) had only one incident record, while 8 946 (9.15%) had 2 or more cases in this period; there were 69 771 (66.06%) patients who only needed to see a doctor once for each disease, 19.92% of the patients needed to be treated twice, and 14 801 (14.02%) patients needed to go to the hospital or clinic three times or more. The incidence of HFMD showed obvious seasonality and periodicity, which mainly concentrated in April to July each year, and the epidemic cycle was 2 years; most of the cases were 1 to 3-year old children, with more cases in male. The incidence density varied across the region, with the highest density observed in Ninghai (4 524.76/100 000 person-years), followed by Xiangshan (3 984.22/100 000 person-years). In 3 748 library-conformed cases, 2 834(75.61%) were detected positive, among which enterovirus-A71, Cox-A16 and other enteroviruses accounted for 9.03%, 31.55% and 59.42%, respectively. During the study period, the cumulative coverage of enterovirus-A71 vaccine increased year by year, with the proportion of enterovirus-A71 and severe cases both gradually decreasing. Conclusion The current status of hand, foot and mouth disease in Ningbo is still serious. Children under 3-year old (especially male children aged 1 year) were the key population for prevention and control. Vaccination might lead to changes in major pathogenic virus type, of which more attention should be paid to the potential impact on disease surveillance, prevention and control.