To determine the effect of active tuberculosis on survival and the incidence of opportunistic infections in HIV-infected patients, we performed a retrospective cohort study at four U.S. medical centers to compare the survival and incidence rate of opportunistic infections in 106 HIV-infected patients with active tuberculosis (cases) with that of 106 HIV-infected patients without tuberculosis (control subjects) but with a similar level of immunosuppression (measured by the absolute CD4+ lymphocyte count) as the cases. Cases and control subjects were similar with regard to age, sex, race, previous opportunistic infection, and use of antiretroviral therapy, but they were more likely than control subjects to have a history of intravenous drug use (49 versus 19%). The mean CD4+ counts were similar for cases and control subjects (154 versus 153 cells/microliters, respectively). The incidence rate of new AIDS-defining opportunistic infections in cases was 4.0 infections per 100 person-months compared with 2.8 infections per 100 person-months in control subjects for an incidence rate ratio (RR) of 1.42 (95% confidence interval: 0.94-2.11). Cases also had a shorter overall survival than did controls subjects (p = 0.001). Active tuberculosis was associated with an increased risk for death (odds ratio = 2.17), even when controlling for age, intravenous drug use, previous opportunistic infection, baseline CD4+ count, and antiretroviral therapy. Although active tuberculosis may be an independent marker of advanced immunosuppression in HIV-infected patients, it may also act as a cofactor to accelerate the clinical course of HIV infection.