In 2001, New York State health officials were notified about 2 patients with Creutzfeldt-Jakob disease who had undergone neurosurgical procedures at the same hospital within 43 days of each other. One patient had Creutzfeldt-Jakob disease at the time of surgery; the other patient developed Creutzfeldt-Jakob disease 6.5 years later. This investigation highlights the difficulties in assessing possible transmission of Creutzfeldt-Jakob disease.