Strain W, a highly drug-resistant strain of Mycobacterium tuberculosis, was responsible for large nosocomial outbreaks in New York in the early 1990s. To describe the spread of strain W outside New York, we reviewed data from epidemiologic investigations, national tuberculosis surveillance, regional DNA fingerprint laboratories, and the Centers for Disease Control and Prevention Mycobacteriology Laboratory to identify potential cases of tuberculosis due to strain W. From January 1992 through February 1997, 23 cases were diagnosed in nine states and Puerto Rico; 8 were exposed to strain W in New York before their diagnosis; 4 of the 23 transmitted disease to 10 others. Eighty-six contacts of the 23 cases are presumed to be infected with strain W; 11 completed alternative preventive therapy. Strain W tuberculosis cases will occur throughout the United States as persons infected in New York move elsewhere. To help track and contain this strain, health departments should notify the Centers for Disease Control and Prevention of cases of tuberculosis resistant to isoniazid, rifampin, streptomycin, and kanamycin.