To evaluate the acceptance and usefulness of a hospital-based tabletop bioterrorism exercise. A descriptive study of responses to a smallpox scenario delivered as a tabletop exercise in three modules. A large, multi-institutional urban health system. Healthcare workers representing 16 hospital departments. Thirty-nine (78%) of 50 invited employees from 4 hospitals participated. Key responses highlighted the importance of pre-event planning in intra-departmental communication, identification of resources for the dependents of healthcare workers, clarification of the chain of command within the hospital, establishment of a link to key governmental agencies, and advanced identification of negative pressure rooms for cohorting large numbers of patients. Almost one-fourth of the participants described their hospital department as poorly prepared for a bioterrorism event of moderate size. At the conclusion of the tabletop, 79% of the participants stated that the exercise had increased their knowledge of preplanning activities. Seventy-nine percent of all participants, 94% of physicians and nurses, and 95% of participants from non-university hospitals ranked the exercise as extremely or very useful. The exercise was completed in 3 1/2 hours and its total direct cost (excluding lost time from work) was 225 dollars (U.S.). Tabletop exercises are a feasible, well-accepted modality for hospital bioterrorism preparedness training. Hospital employees, including physicians and nurses, rank this method as highly useful for guiding preplanning activities. Infection control staff and hospital epidemiologists should play a lead role in hospital preparedness activities. Further assessment of the optimal duration, type, and frequency of tabletop exercises is needed.