Objective: To evaluate the effectiveness of varicella vaccine in varicella outbreaks and to analyze the influencing factors, and to provide a reference for making the targeted prevention and controlling measures. Methods: A total of 3 888 students with no history of varicella were selected from 2 schools with varicella outbreak in Guangdong Province in 2021, a retrospective cohort study was conducted by using questionnaire survey, rate ratio ( RR ) and vaccine effectiveness ( VE ) values were calculated and Logistic regression was uses to analyze the factors influencing the protective effect of varicella. Results: There were 138 confirmed cases of varicella among the participants. There was no significant sex difference in the vaccination rate( χ 2=1.36, P =0.51), but there was significant difference in the vaccinattion rate of different age groups( χ 2=555.82, P <0.01). The overall protective effect of VarV was 66.94%(95% CI =56.17%-77.71%), and the protective effect of 2 doses of vaccine( VE = 90.02% , 95% CI =83.13%-96.90%) was higher than that of 1 dose( VE =49.40%, 95% CI =32.36%-66.44%)( χ 2=24.93, P < 0.01 ). The high fever rates in the vaccinated and unvaccinated groups were 7.69% and 25.81%, with significant difference( χ 2= 6.29 , P <0.05). The rates of moderate and severe skin lesions of vaccinated and unvaccinated groups was 20.00% and 50.00%, respectively, and the difference was statistically significant( χ 2=11.32, P <0.01). The protective effects of varicella vaccine against high fever and moderate to severe rash were 70.19%(95% CI =42.11%-98.27%) and 60.00%(95% CI =38.15%-81.85%). Stratified analysis showed that there were significant differences in different years of vaccination( χ 2=37.87, P <0.05), while there were no significant differences in age of vaccination and vaccine manufacturer ( P >0.05). Conclusion Varicella vaccination can prevent chickenpox infection and reduce the severity of the disease. However, the efficacy of varicella vaccine was affected by vaccination years. It is recommended to improve the vaccination coverage of varicella vaccine to prevent the outbreak of the epidemic.