Although varicella vaccine is given to clinically stable human immunodeficiency virus (HIV)-infected children, its effectiveness is unknown. We assessed its effectiveness by reviewing the medical records of closely monitored HIV-infected children, including those receiving highly active antiretroviral therapy (HAART) between 1989 and 2007. Varicella immunization and development of varicella or herpes zoster were noted. Effectiveness was calculated by subtracting from 1 the rate ratios for the incidence rates of varicella or herpes zoster in vaccinated versus unvaccinated children. The effectiveness of the vaccine was 82% (95% confidence interval [CI], 24%-99%; P = .01) against varicella and was 100% (95% CI, 67%-100%; P < .001) against herpes zoster. When the analysis was controlled for receipt of HAART, vaccination remained highly protective against herpes zoster.