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HIV–tuberculosis (TB) co-infection remains an important cause of mortality in sub-Saharan Africa. Clinical trials have reported early (within 2 weeks of TB therapy) antiretroviral therapy (ART) reduces mortality among HIV–TB co-infected research participants with low CD4+ cell counts, but this has not been consistently observed. We aimed to evaluate the current WHO recommendations for ART in HIV–TB co-infected patients on mortality in routine clinical settings.We compared two cohorts before (2008–2010) and after (2012–2013) policy change on ART timing after TB and examined the effectiveness of early versus delayed ART on mortality in HIV–TB co-infected participants with CD4+ cell count 100 cells/μl or less. We used inverse probability censoring-weighted Cox models on baseline characteristics to balance the study arms and generated hazard ratios for mortality.Of 356 participants with CD4+ cell counts 100 cells/μl or less, 180 were in the delayed ART cohorts whereas 176 were in the early ART cohorts. Their median age (32.5 versus 32 years) and baseline CD4+ cell counts (26.5 versus 26 cells/μl) respectively were similar. There was no difference in mortality rates of both cohorts. The risk of death increased in participants with a positive Cryptococcal antigen (CrAg) test in both the early ART cohort (aHR = 2.6, 95% CI 1.0–6.8; P = 0.045) and the delayed ART cohort (aHR = 4.2, 95% CI 1.9–9.0; P < 0.001Early ART in patients with HIV–TB co-infection was not associated with reduced risk of mortality in routine care. Asymptomatic Cryptococcal antigenaemia increased the risk of mortality in both cohorts.