OBJECTIVES: Economic analysis is an important component in formulating national policy. We evaluated the economic impact of hepatitis A vaccination of all US children ages 12 to 23 months as compared with no vaccination and with current implementation of the preexisting (issued in 1999), regional policy. METHODS: We developed a Markov model of hepatitis A that followed a single cohort from birth in 2005 through death or age 95 years. From the societal perspective, the model compared the outcomes that resulted from routine vaccination at age 1 year to 2 scenarios: no hepatitis A vaccination and hepatitis A vaccination at levels observed in 2003 under the preexisting policy. We evaluated the economic impact of vaccination nationwide, in areas where vaccination was already recommended, and in areas where no previous recommendation existed. RESULTS: Without childhood vaccination, the approximately 4 million children in the 2005 birth cohort would be expected over their lifetimes to have 199,000 hepatitis A virus infections, including 74,000 cases of acute hepatitis A and 82 deaths, resulting in 134 million dollars in hepatitis A-related medical costs and productivity losses. Compared with no vaccination, routine vaccination at age 1 year would prevent 172,000 infections, at a cost of 28,000 dollars per quality-adjusted life year saved. Compared with maintaining the levels of hepatitis A vaccination under the preexisting regional policy, routine vaccination at age 1 year would prevent an additional 112,000 infections, at a cost of 45,000 dollars per quality-adjusted life year saved. CONCLUSIONS: The cost-effectiveness of nationwide hepatitis A vaccination compared with no vaccination, and the incremental cost-effectiveness of this recommendation compared with preexisting recommendations, is similar to that of other accepted public health interventions. In October 2005, the Advisory Committee on Immunization Practices recommended extending hepatitis A immunization to all US children ages 12 to 23 months.