Objectives: Health benefits and costs of combined reduced-antigen-content tetanus, diphtheria, and pertussis (Tdap) immunization among adults ≥65 years have not been evaluated. In February 2012, the Advisory Committee on Immunization Practices (ACIP) recommended expanding Tdap vaccination (one single dose) to include adults ≥65 years not previously vaccinated with Tdap. Our study estimated the health and economic outcomes of one-time replacement of the decennial tetanus and diphtheria (Td) booster with Tdap in the 10% of individuals aged 65 years assumed eligible each year compared with a baseline scenario of continued Td vaccination. Methods: We constructed a model evaluating the cost-effectiveness of vaccinating a cohort of adults aged 65 with Tdap, by calculating pertussis cases averted due to direct vaccine effects only. Results are presented from societal and payer perspectives for a range of pertussis incidences (25–200 cases per 100,000), due to the uncertainty in estimating true annual incidence. Cases averted were accrued throughout the patient 's lifetime, and a probability tree used to estimate the clinical outcomes and costs (US2010)foreachcase.Quality−adjustedlife−years(QALYs)losttoacutediseasewerecalculatedbymultiplyingcasesofmild/moderate/severepertussisbytheassociatedhealth−statedisutility;QALYlossesduetodeathandlong−termsequelaewerealsoconsidered.IncrementalcostsandQALYsweresummedoverthecohorttoderiveincrementalcost−effectivenessratios.Scenarioanalysesevaluatedtheeffectofalternativeplausibleparameterestimatesonresults.Results:Atincidencelevelsof25,100,200cases/100,000,vaccinatingadultsaged65yearscostsanadditional336,000, 63,000and17,000/QALY gained, respectively. Vaccination has a cost-effectiveness ratio less than $50,000/QALY if pertussis incidence is >116 cases/100,000 from societal and payer perspectives. Results were robust to scenario analyses. Conclusions: Tdap immunization of adults aged 65 years according to current ACIP recommendations is a cost-effective health-care intervention at plausible incidence assumptions