OBJECTIVES:   To estimate the cost-effectiveness of the recommended US pediatric vaccination schedule from a public health perspective. METHODS: An Excel-based cost-effectiveness calculator was constructed for the current pediatric vaccine schedule including: diphtheria, tetanus, and pertussis (DTaP), measles, mumps, and rubella (MMR), polio, hepatitis A, hepatitis B, haemophilus influenza B (Hib), varicella, pneumococcal, adolescent meningococcal, influenza, human papillomavirus (HPV) and rotavirus vaccines. Estimates of the incremental direct medical costs and quality-adjusted life-years (QALYs) for vaccination versus no vaccination were obtained from published literature. Where estimates were not available, a decision tree was constructed to model QALYs gained per vaccinated child. The tree includes branches for disease incidence pre- and post-vaccine introduction, case-fatality, and permanent, serious sequelae. 2008-2009 vaccination coverage and 2009 prices were used to estimate vaccine costs.  Estimates of lifetime costs and QALYs per vaccinated child, discounted at 3% annually, were applied to a US birth cohort, assuming direct effects only. Costs are expressed in 2009 US$.   Incremental costs and QALYs for individual vaccines and the whole schedule were evaluated.   The model assessed schedule completion with single disease vaccines as well as completion with two different pentavalent combination vaccines (DTaP, polio, Hib or DTap, polio, hepatitis B) plus single disease vaccines. RESULTS:   Regardless of how the current pediatric vaccine schedule is completed, annual estimated cost savings range between $13.8 billion to $14.3 billion.  DTaP, MMR, polio, Hib and HPV are cost-saving, as are both pentavalent vaccines.   Other single-disease vaccines add cost but contribute to a total of 1.4M QALYs gained per year.  CONCLUSIONS: The current US pediatric vaccine schedule is estimated to be cost-saving and to provide substantial benefits in quality-adjusted survival. Use of combination vaccines increases the savings. Neither herd immunity nor indirect costs were considered in the model; their inclusion likely would increase the estimated cost savings.