Using a stochastic simulation model of influenza transmission, clinical illness, and economic costs, we estimated the population-wide benefits of routinely vaccinating US children (ages 6 months to 18 years) against influenza. Disease burden was projected to decline as a result of both reduced susceptibility to infection among vaccinees and reductions in disease transmission to others in the community. Vaccination of 20% of children would reduce the total number of influenza cases in the US by 46%; 80% coverage would reduce the total number of cases by 91%. Similar reductions were estimated to occur in influenza-related mortality and economic costs.