OBJECTIVE: To assess the impact of outbreaks of Bordetella pertussis infection on a tertiary care medical system. DESIGN: Retrospective study. SETTING: Academic tertiary care medical center and affiliated ambulatory care settings. SUBJECTS: All patients and healthcare workers (HCWs) who were in close contact with patients with laboratory-confirmed cases of B. pertussis infection from October 1, 2003, through September 30, 2004. INTERVENTION: Direct and indirect medical center costs were determined, including low and high estimates of time expended in the evaluation and management of exposed patients and HCWs during outbreak investigations of laboratory-confirmed cases of B. pertussis infection. RESULTS: During this period, 20 primary and 3 secondary laboratory-confirmed cases of B. pertussis infection occurred, with 2 primary pertussis cases and 1 secondary case occurring in HCWs. Outbreak investigations prompted screening of 353 medical center employees. Probable or definitive exposure was identified for 296 HCWs, and 287 subsequently received treatment or prophylaxis for B. pertussis infection. Direct medical center costs for treatment and prophylaxis were $13,416 and costs for personnel time were $19,500-$31,190. Indirect medical center costs for time lost from work were $51,300-$52,300. The total cost of these investigations was estimated to be $85,066-$98,456. CONCLUSIONS: Frequent B. pertussis exposures had a major impact on our facility. Given the impact of exposures on healthcare institutions, routine vaccination for HCWs may be beneficial.