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Mortality in patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB) is high, particularly in sub-Saharan Africa. This study aimed to compare mortality and predictors of mortality in those who were antiretroviral therapy (ART) naïve to those with prior ART exposure.This retrospective cohort study was conducted in Serowe/Palapye District, Botswana, a predominantly urban district with a large burden of HIV-associated TB with a high case fatality. Between January 1, 2013 and December 31, 2013, patients confirmed with HIV-associated TB were enrolled and followed up. Kaplan–Meier and Cox proportional hazard modeling was undertaken to identify predictors of mortality, with ART initiation included as time-updated variable.Among the 300 patients enrolled in the study, 131 had started ART before TB diagnosis (44%). There were 45 deaths. There was no difference in mortality between ART-naïve patients and those with prior ART exposure. In the multivariate analysis, no ART use during TB treatment (hazard ratio [HR] = 5.6, 95% confidence interval [CI] = 2.9–11; P < .001), opportunistic infections other than TB (HR = 8.5, 95% CI = 4–18.4; P = .013), age ≥60 years (HR = 4.8, 95% CI = 1.8–13; P = .002), hemoglobin <10 g/dL (HR = 2.4, 95% CI = 1.3–4.5) and hepatotoxicity (HR = 5, 95% CI = 1.6–17; P = .007) were associated with increased mortality. In the subgroup analysis, among ART-naïve patients, no ART use during TB treatment (HR = 8.1, 95% CI = 3.4–19.4; P < .001), opportunistic infections other than TB (HR = 16, 95% CI = 6.2–42; P < .001), and hepatotoxicity (HR = 8.3, 95% CI = 2.6–27; P < .001) were associated with mortality. Among patients with prior ART exposure, opportunistic infections other than TB (HR = 6, 95% CI = 2.6–27; P < .001) were associated with mortality.Mortality in patients with HIV-associated TB is still high. To reduce mortality, close clinical monitoring of patients together with initiation of ART during TB treatment is indicated.