Pertussis is increasingly recognized as a source of infection in adults who then commonly infect young children. Immunity to illness caused by Bordetella pertussis is not long-lived, so optimal control of pertussis may require booster immunizations. In a cost-benefit analysis, we evaluated the benefits of 7 independent strategies for administering a pertussis booster, in the form of a diphtheria-tetanus-acellular pertussis vaccine, to adolescents and adults. Break-even vaccine costs for each strategy were calculated by dividing costs preventable by vaccine by the number of persons eligible for vaccination. Of these strategies, the most economical would be to immunize adolescents 10–19 years of age, which would prevent 0.7–1.8 million pertussis cases and save $0.6- $1.6 billion over a decade. Although justified by our analysis, routine adult booster vaccinations every decade would be more expensive and more difficult to implement. A recommendation for booster vaccinations every 10 years requires more information about duration of immunity, program costs, compliance, and nonmedical costs associated with pertussis.