Background. Because of ongoing outbreaks of varicella, a second dose of varicella vaccine was added to the routine immunization schedule for children in June 2006 by the Centers for Disease Control and Prevention.

Methods. We assessed the effectiveness of 2 doses of varicella vaccine in a case-control study by identifying children ≥4 years of age with varicella confirmed by polymerase chain reaction assay and up to 2 controls matched by age and pediatric practice. Effectiveness was calculated using exact conditional logistic regression.

Results. From July 2006 to January 2010, of the 71 case subjects and 140 matched controls enrolled, no cases (0%) vs 22 controls (15.7%) had received 2 doses of varicella vaccine, 66 cases (93.0%) vs 117 controls (83.6%) had received 1 dose, and 5 cases (7.0%) vs 1 control (0.7%) did not receive varicella vaccine (P < .001). The effectiveness of 2 doses of the vaccine was 98.3% (95% confidence level [CI]: 83.5%–100%; P < .001). The matched odds ratio for 2 doses vs 1 dose of the vaccine was 0.053 (95% CI: 0.002–0.320; P < .001).

Conclusion. The effectiveness of 2 doses of varicella vaccine in the first 2.5 years after recommendation of a routine second dose of the vaccine for children is excellent. Odds of developing varicella were 95% lower for children who received 2 doses compared with 1 dose of varicella vaccine.