Twenty-nine healthcare workers (HCW) were exposed to an active case of unrecognized drug-susceptible pulmonary tuberculosis in a community hospital for as long as 2 h in the emergency room and 10 h in a medical intensive care unit. Twelve of the 29 exposed HCW could not be evaluated for tuberculosis infection because 10 of them had a previously positive tuberculin skin test and two were lost to follow-up. Of the remaining 17 tuberculin skin test negative HCW, 13 (76%) either converted their skin test to positive (10 HCW) or developed active disease (three HCW) after exposure to the index case. The Mycobacterium tuberculosis isolates from the three HCW had identical DNA restriction fragment length polymorphism (RFLP) patterns when studied by pulsed field gel electrophoresis. This case of drug-susceptible tuberculosis was associated with unusually high rates of tuberculosis infection and disease in HCW. Prevention of similar occurrences in HCW may be difficult because of the short exposure time required for transmission of tuberculosis and the absence of consensus on optimal respiratory protective measures.