Hemophilus influenzae type b (HIB) is the leading cause of bacterial meningitis in the United States. Efforts are under way to develop vaccines immunogenic in children younger than 18 months, but clinical efficacy of a previously developed HIB polysaccharide vaccine has already been established in children aged 18 months or older. We developed a cost-effectiveness model to evaluate immunizing US children with this HIB polysaccharide vaccine pending development of a more immunogenic product. The model permitted comparison of the impact of alternative strategies for use of the vaccine, including universal use at 18 or 24 months of age, use of a second dose after primary immunization, and use in high-risk groups such as day-care-center attendees. Universal vaccination at 18 or 24 months of age resulted in similar estimates of disease prevented, as a consequence of the higher expected efficacy and duration of immunity for the vaccine when given at 24 months. Overall, the implementation of routine childhood immunization against HIB at 18 months of age was the most cost-effective strategy. Universal vaccination at 18 months of age combined with a second dose for day-care-center attendees would substantially increase the number of cases prevented, with a minimal increase in costs. Universal vaccination with a two-dose schedule beginning at 18 months of age could prevent the most disease.