Intra-institutional spread of tuberculosis (Tb) has re-emerged as a substantial public and occupational health threat. To characterize the person-hours and lifetime risks of Tb-related morbidity and mortality, we performed a risk assessment for health care workers (HCWs) developing Tb-related morbidity and mortality at varying levels of exposure, engineering controls, and respiratory protection. Under average conditions of exposure, one Tb skin-test conversion is estimated to occur for every 2650 person-hours of work by unprotected workers. With higher exposures, a skin-test conversion for an unprotected worker may occur in as few as 3 person-hours. Use of respiratory protection is estimated to reduce risks by the following proportions: surgical mask, 2.4-fold; disposable dust, fume, mist, or disposable high-efficiency particulate air filtering (HEPA) mask, 17.5-fold; elastomeric HEPA cartridge respirator, 45.5-fold; or powered air-purifying respirator (PAPR), 238-fold. Assuming a lifetime exposure of 250 hours, the risk of a skin-test conversion is estimated to be 9%. We conclude that HCWs are at substantial risk for Tb-related morbidity and mortality, and that administrative controls, engineering controls, and respirators offer substantial benefits in risk reduction.