The effectiveness of varicella vaccination strategies needs to be further evaluated. The vaccine effectiveness (VE) of the varicella vaccine was evaluated, and changes in VE of varicella vaccination in primary and secondary school students in Qingdao, China, over time were analyzed.

We conducted a 1:3 matched case–control study, using data from the Chinese Information System for Disease Control and Prevention, Qingdao Student Health Examination Management System, and Qingdao Immunization Program Information System. VE of the varicella vaccination was estimated using conditional logistic regression modeling.

A total of 3,249 varicella cases and 9,747 matched controls were included. One- and two-dose varicella vaccination had VE of 31.95 % (95 % confidence interval [CI]: 25.05 %–38.20 %) and 82.02 % (95 % CI: 78.33 %–85.07 %), respectively, and the incremental VE (two-dose versus one-dose vaccination) was 73.57 % (95 % CI: 68.26 %–78.00 %). VE remained at 71.46 % 10 years after the two-dose varicella vaccination, compared with a considerable decrease in VE to 29.73 % approximately 3–5 years after the one-dose varicella vaccination. VE of two-dose varicella vaccination was not related to the time interval between the two doses. The risk of varicella infection decreases with the number of doses of varicella vaccine received and with the age at which the first dose is given and increases with time after the last dose.

Two-dose varicella vaccination provides better protection for children and is therefore recommended for inclusion in China’s national immunization program.