SETTING: Human immunodeficiency virus (HIV) infected patients followed in a large cohort in Rio de Janeiro, Brazil. OBJECTIVE: To evaluate the association of tuberculosis (TB) and other covariables with non-TB-related (NTR) causes of death (CODs). DESIGN: Patients aged .18 years were followed from 1997 to 2009, until death or 31 December 2009, whichever was earlier. CODs were ascertained using a standardised algorithm. TB diagnosis and prophylaxis followed Brazilian guidelines. Poisson models were used to calculate adjusted rate ratios (aRRs). RESULTS: Of 2887 patients included in the study, 761 had TB (26.4%). NTR death rates were twice as high among patients with TB (4/100 vs. 2.09/100 patientyears). TB was associated with NTR deaths (aRR 1.4, 95%CI 1.05–1.86, P ¼ 0.01). Highly active antiretroviral treatment (HAART) was protective against NTR (aRR 0.46, 95%CI 0.34–0.61, P , 0.001). Among patients who had never had active TB, prophylaxis was also protective against NTR (aRR 0.45, P ¼ 0.04). The CD4 cell count increase was very modest for both TB and NTR CODs compared to those who did not die (0 vs. 249 cells, P , 0.001). CONCLUSIONS: TB was significantly associated with increased NTR CODs, indicating rapid progression of disease and increased long-term risk of mortality, probably related to persistent immunodeficiency or incomplete immune recovery. Our results confirm the benefits of HAART and TB prophylaxis.