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In September 2003, 17 symptomatic cases of pertussis among health care workers (HCWs) resulted from a 1-day exposure to an infant who was later confirmed to have pertussis. These HCWs identified 307 close contacts. The hospital implemented extensive infection-control measures. The objective of this study was to determine direct and indirect costs incurred by the hospital and symptomatic HCWs as a result of the September 2003 outbreak and to estimate possible benefits of vaccinating HCWs from the hospital perspective.We determined costs by interviewing infection-control and hospital personnel, reviewing billing records, and surveying symptomatic HCWs. We calculated the benefits and costs of a vaccination program for HCWs, using a probabilistic model to estimate the number of pertussis exposures that would require control measures annually. Sensitivity and threshold analyses were performed.The outbreak cost to the hospital was $74,870. The total measured cost of the outbreak was $81,382, including costs incurred by HCWs ($6512). Our model predicted that vaccinating HCWs against pertussis would prevent >46% of exposures from HCWs with pertussis per year and would provide net savings. The benefit for the hospital was estimated to be 2.38 times the dollar amount invested in vaccinating HCWs. The number of exposures prevented and the benefit-cost ratio were sensitive to the number of exposures identified, the incidence of pertussis among HCWs, and HCW turnover.A single nosocomial pertussis outbreak resulted in substantial disruption and costs to the hospital and to HCWs. Our model suggests that cost savings and benefits could be accrued by vaccinating HCWs against pertussis.