Context. The US Food and Drug Administration approved a meningococcal conjugate A/C/Y/W-135 vaccine (MCV-4) for use in persons aged 11 to 55 years in January, 2005; licensure for use in younger age groups is expected in 2 to 4 years.

Objective. To evaluate and compare the projected health and economic impact of MCV-4 vaccination of US adolescents, toddlers, and infants.

Design. Cost-effectiveness analysis from a societal perspective based on data from Active Bacterial Core Surveillance (ABCs) and other published and unpublished sources. Sensitivity analyses in which key input measures were varied over plausible ranges were performed.

Setting and Patients. A hypothetical 2003 US population cohort of children 11 years of age and a 2003 US birth cohort.

Interventions. Hypothetical routine vaccination of adolescents (1 dose at 11 years of age), toddlers (1 dose at 1 year of age), and infants (3 doses at 2, 4, and 6 months of age). Each vaccination scenario was compared with a “no-vaccination” scenario.

Main Outcome Measures. Meningococcal cases and deaths prevented, cost per case prevented, cost per life-year saved, and cost per quality-adjusted life-year saved.

Results. Routine MCV-4 vaccination of US adolescents (11 years of age) would prevent 270 meningococcal cases and 36 deaths in the vaccinated cohort over 22 years, a decrease of 46% in the expected burden of disease. Before program costs are counted, adolescent vaccination would reduce direct disease costs by $18 million and decrease productivity losses by$50 million. At a cost per vaccination (average public-private price per dose plus administration fees) of $82.50, adolescent vaccination would cost society$633000 per meningococcal case prevented and \$121000 per life-year saved. Key variables influencing results were disease incidence, case-fatality ratio, and cost per vaccination. The cost-effectiveness of toddler vaccination is essentially equivalent to adolescent vaccination, whereas infant vaccination would be much less cost-effective.

Conclusions. Routine MCV-4 vaccination of US children would reduce the burden of disease in vaccinated cohorts but at a relatively high net societal cost. The projected cost-effectiveness of adolescent vaccination approaches that of recently adopted childhood vaccines under conditions of above-average meningococcal disease incidence or at a lower cost per vaccination.