Hepatitis A is an important public health problem in Chile. Childhood vaccination has reduced hepatitis A rates in several countries, prompting this evaluation of its cost-effectiveness in Chile. Using a Markov model, we project mass vaccination would reduce hepatitis A cases among birth cohort members and their personal contacts >80%. Vaccination costs of US$ 5.3-6.4 million would be offset by US$ 9.2-9.4 million reductions in disease costs. Further, approximately 70 fatal infections would be averted and >4600 quality-adjusted life years would be saved. This analysis supports the cost-effectiveness of universal childhood hepatitis A vaccination in Chile.