A 2-dose vaccination against varicella has been adopted in many places; however, it has not been widely introduced in Korea. This study aimed to assess 1-dose and 2-+dose vaccine effectiveness (VE) against laboratory-confirmed varicella in Korea to provide a scientific basis for developing an immunization strategy.We constructed a national cohort using national surveillance data and the national immunization registry. From the cohort, we conducted a 1:2 matched nested case-control study to estimate and compare the VE of the 1-dose and 2-dose of varicella vaccination using exact conditional logistic regression. VE was calculated as [1 - matched odds ratio (OR) × 100%].From January 1, 2011 to December 31, 2020, a total of 205,173 varicella cases were reported to the notifiable diseases surveillance system. Of these, we included 4,387 laboratory-confirmed varicella cases and 8,774 controls for the analyses. The VE of 1-dose vaccination was 16.8% (95% CI: -9.0% to 36.5%), whereas the VE of 2-doses of the vaccination was 98.6% (95% CI: 96.0%-99.5%).These findings suggest that the 2-dose vaccination strategy can be an effective strategy to prevent varicella.