Evidence regarding the effect of tuberculosis (TB) on HIV disease progression at the population level remains inconclusive. We estimated the effect of incident TB on time to AIDS-related death, using a marginal structural Cox model. Between 1984 and 2005, 2882 HIV-infected men in the Multicenter AIDS Cohort Study contributed 21 914 person-years while followed for a median of 5.4 years. At study entry, the median CD4 cell count and HIV-1 RNA viral load were 533 cells/microl (interquartile range: 365-737) and 12, 953 copies/ml (interquartile range: 2453-48 540), respectively. This study was performed in a setting with a modest exposure to HAART; 8295 of 23 801 (35%) person-years were followed during the HAART era. Fifteen men incurred incident TB, yielding a TB incidence of 7 (95% confidence interval: 4-14) per 10 000 person-years and 1072 died of AIDS-related causes. Accounting for potential confounders, including CD4 cell count and viral load, the hazard of AIDS-related death was 2.4 times more for the person-time with TB compared to the person-time without TB (95% confidence interval: 1.2-4.7). Results underscore the importance of avoiding TB by using preventive interventions such as treatment of latent TB infection, particularly in populations with a large prevalence of HIV/TB co-infected individuals.