It is important to minimize the costs and risks associated with unnecessary prophylaxis of health care workers. We studied the process of providing rabies postexposure prophylaxis following the 24-day hospitalization of a rabies-infected patient. Of 209 persons who cared for the patient, only 12 (6%) reported high-risk contact, and treatment was recommended for them. Unnecessary prophylaxis was limited to 35 persons (18%) who did not report high-risk contacts but who requested treatment because of their uncertainty about the degree of exposure. These persons, however, spent significantly more time with the patient compared with persons who did not request treatment. Maintaining strict isolation precautions when rabies is being considered, educating employees about the risks of transmission in this setting, carefully documenting exposures, and adhering to the guidelines for postexposure prophylaxis may help reduce excessive prophylaxis of health care workers.