OBJECTIVES: To evaluate the healthcare and economic impact of routine hepatitis A vaccination of toddlers in Chile. METHODS: We used a dynamic model of hepatitis A infection to evaluate the impact of a two-dose vaccination program, administered at age 12 and 18 months. The model incorporated the changing epidemiology of hepatitis A in Chile and the development of vaccine-induced herd immunity. Our analysis was conducted from the Ministry of Health perspective and an estimation of the societal perspective was done. RESULTS: Vaccination of toddlers rapidly reduced the healthcare burden of hepatitis A. In the base case (95% vaccination coverage, 100-year time horizon, 1% annual decrease in force of infection), the average number of infections fell by 76.6% annually, and associated deaths fell by 59.7%. Even at 50% coverage, the program reduced infection rates substantially. Routine vaccination of toddlers had economic as well as health benefits, saving US$4 984 per life-year gained (base case scenario). The program became cost-saving after 6 years, and its overall cost-effectiveness per life-year gained was largely unaffected by changes in disease-related costs, herd immunity, coverage rate, and annual decrease in force of infection. CONCLUSION: Routine vaccination of toddlers will reduce rates of symptomatic hepatitis A and associated mortality. The cost of the two-dose schedule evaluated here will be less expensive than disease-related costs in the absence of vaccination from the sixth year of its implementation. These findings support the establishment of a routine vaccination program for toddlers in Chile to reduce the healthcare and economic burden of hepatitis A.