Noroviruses are enterically transmitted and are a frequent cause of gastroenteritis, affecting 23 million people annually in the United States. We describe a norovirus outbreak and its control in a tertiary care hospital during February-May 2004.Patients and health care workers met the case definition if they had new onset of vomiting and/or diarrhea during the outbreak period. Selected stool samples were tested for norovirus RNA. We also determined outbreak costs, including the estimated lost revenue associated with unit closures, sick leave, and cleaning expenses.We identified 355 cases that affected 90 patients and 265 health care workers and that were clustered in the coronary care unit and psychiatry units. Attack rates were 5.3% (7 of 133) for patients and 29.9% (29 of 97) for health care workers in the coronary care unit and 16.7% (39 of 233) for patients and 38.0% (76 of 200) for health care workers in the psychiatry units. Thirteen affected health care workers (4.9%) required emergency department visits or hospitalization. Detected noroviruses had 98%-99% sequence identity with representatives of a new genogroup II.4 variant that emerged during 2002-2004 in the United States (e.g., Farmington Hills and other strains) and Europe. Aggressive infection-control measures, including closure of units and thorough disinfection using sodium hypochlorite, were required to terminate the outbreak. Costs associated with this outbreak were estimated to be $657,644.The significant disruption of patient care and cost of this single nosocomial outbreak support aggressive efforts to prevent transmission of noroviruses in health care settings.