Hematopoietic stem cell transplantation (HSCT) results in impaired cell-mediated immunity, which subsequently increases the risk of infection from bacterial, fungal, and viral pathogens. Mycobacterial infections are commonly seen in immunodeficient patients, especially in endemic areas. Several series that have reviewed mycobacterial infections in HSCT patients reported incidences varying from less than 0.1% to 5.5%. From February 1996 to July 2003, we retrospectively reviewed records of 295 adult patients who underwent HSCT at Samsung Medical Center, Korea. Mycobacterial infections were diagnosed in 9 (3.1%) of the 295 transplant recipients. The time from HSCT to tuberculosis (TB) infection ranged from 45 days to 165 days posttransplantation. Analysis at the univariate level indicated that a conditioning regimen with total body irradiation (TBI), chronic graft-versus-host disease, and a previous history of TB infection were significant risk factors for the development of TB infection after HSCT. Multivariate analysis revealed that only a previous history of TB infection and TBI increased the risk of TB infection in HSCT patients (relative risk, 4.8 and 12.5, respectively). Isoniazid prophylaxis in HSCT recipients with only radiologic findings suggestive of past inactive TB infection did not significantly alter the incidence of TB infections (P = .236). In conclusion, a previous history of active TB infection and TBI were significant risk factors of TB infection following HSCT, and isoniazid prophylaxis may benefit HSCT recipients with a previous history of active TB infection.