A nosocomial outbreak of Mycobacterium tuberculosis Beijing/W genotype infected 15 healthcare workers (HCWs) in a medical center in Taiwan, where there is a high prevalence of tuberculosis and a high rate of positive tuberculin skin tests. An index patient with laryngeal cancer and a lung abscess was identified by epidemiological investigation and it was found that an M. tuberculosis isolate from his lung tissue sample had an identical IS6110 restriction fragment length polymorphism pattern to the isolates from 3 HCWs. Confirmation of the identity of this strain as Beijing/W genotype was made using spoligotyping. Seven hundred and eighty-five HCWs potentially exposed to the probable index patient received contact investigation and chest X-ray screening. We used chest high-resolution computed tomography (HRCT) to clarify trivial lesions in chest X-rays. Nine HCWs with smear-negative pulmonary tuberculosis were diagnosed by HRCT. Fifteen of the 35 (42.9%) HCWs with documented exposure to the index patient developed pulmonary tuberculosis within 11 months after exposure. The outbreak was successfully controlled by active case finding and enforcement of infection control strategies. Intervention to detect the potential tuberculosis source is helpful in the prevention and control of a nosocomial tuberculosis outbreak. HRCT can be a useful tool for tuberculosis diagnosis of contacts in an outbreak situation.