OBJECTIVES: To assess the population-level impact and cost-effectiveness of universal Hepatitis A vaccination of children in United States as recommended  by Advisory Committee on Immunization Practices (ACIP) in 2006 compared with the prior ACIP regional policy of routine vaccination of children living in states with high hepatitis rates. METHODS: We developed a population-dynamic model of Hepatitis A to evaluate the public health- and economic- impacts of two-dose Hepatitis A vaccination of children 12 and 18 months of age. The dynamic model was fitted to Hepatitis A seroprevalence from the National Health and Nutrition Examination Survey (NHANES II and III) and reported incidence from the National Notifiable Diseases Surveillance System (1980–1995). We used a societal perspective and projected outcomes over the period 2006­–2106 (a 100-year time horizon). Both costs and quality-adjusted life years (QALYs) were discounted at 3% per year. RESULTS: Universal Hepatitis A vaccination prevented 144,375 infections, 63,153 outpatient visits, 2,727 hospitalizations, and 96 deaths incrementally on an average annual basis when compared to the regional vaccination policy. Herd protection played an important role in reducing infections as it accounted for prevention of nearly 76% of deaths and 50% of outpatient visits and hospitalizations. Ignoring herd protection, vaccination prevented 90,845 infections, 34,353 outpatient visits, 1,438 hospitalizations, and 23 deaths annually. Taking herd protection into account, universal vaccination was cost saving, whereas without it the ICER was $41,712/QALY. CONCLUSIONS: Universal two-dose vaccination of children led to significant reductions in Hepatitis A mortality and morbidity.  Consequently, universal vaccination was cost saving compared with a regional vaccination policy. Herd protection effects of vaccination programs had a significant impact on hepatitis A mortality, morbidity, and cost-effectiveness ratios. Because of their ability to capture the natural phenomenon of herd protection, dynamic models have significant utility for economic evaluation of Hepatitis A vaccination programs.