Objective: To investigate the epidemiological characteristics of varicella in Yandu District, Yancheng City, Jiangsu Province from 2005 to 2021, so as to provide insights into the improvements of the varicella control strategy. Methods: The data pertaining to cases in Yandu District from 2005 to 2021 were captured from the National Notifiable Diseases Network Reporting System, and the coverage of varicella vaccination in Yandu District from 2016 to 2021 was captured from the Jiangsu Provincial Immunization Planning System. The trends in incidence of varicella were analyzed using annual percent change (APC), the temporal, population and spatial distributions of varicella cases were descriptively analyzed, and the correlation between the cumulative first-dose varicella vaccination rate and incidence of varicella was examined among birth cohorts in Yandu District from 2005 to 2021. Results: Totally 6 144 varicella cases were reported in Yandu District from 2005 to 2021, with annual mean reported incidence of 50.05/105. The incidence of varicella appeared a tendency towards a rise in Yandu District from 2012 to 2018, with APC of 77.97% (t=11.702, P<0.001), and the incidence appeared a tendency towards a decline from 2018 to 2021, with APC of -41.93% (t=-6.911, P<0.001). The incidence of varicella peaked during the period between November and January of the following year (45.95%), and during the period between May and June (20.35%). The mean incidence of varicella was higher among men than among women (54.72/105 vs. 45.00/105; χ2=57.858, P<0.001). The highest incidence of varicella was found among cases at ages of 6 to 9 years (543.78/105), and varicella predominantly occurred among primary school students (38.40%) and pre-school children (31.85%), with high annual mean incidence in the eastern urban areas (74.27/105).The cumulative first-dose varicella vaccination rate negatively correlated with the incidence of varicella among the birth cohorts in Yandu District in 2019 (r=-0.501, P<0.001), 2020 (r=-0.646, P<0.001) and 2021 (r=-0.602, P<0.001). Conclusions The incidence of varicella appeared a tendency towards a rise followed by a reduction in Yandu District from 2005 to 2021, and the incidence of varicella peaked in winter and at the turn from spring to summer, with varicella predominantly found among primary school students and preschool children.