The purpose of this study was to identify clinical and epidemiological factors associated with death in patients with an in-hospital diagnosis of tuberculosis (TB), in a city with a high prevalence of TB and human immunodeficiency virus (HIV) infection. The study was a retrospective, cohort study conducted at a general, tertiary-care, university-affiliated hospital. Patients who began treatment for TB after hospitalization were included. Predictors of mortality were assessed. The primary outcomes were the in-hospital mortality and the mortality after discharge. We evaluated the medical records of 311 patients with TB. The overall mortality rate of all study participants was 99/311 (31.8%). The mortality rates during hospitalization and after discharge were 50/311 (16.1%) and 49/261 (18.8%), respectively. Mechanical ventilation, consolidation in chest X-ray, and negative sputum smear were predictors of in-hospital death in multivariate analysis. Independent predictors of mortality after discharge in multivariate analysis included total duration of hospitalization and being a current smoker. We found a high overall mortality rate for patients hospitalized with TB in a region with a high prevalence of TB and HIV. The risk of mortality once patients with TB are hospitalized is unlikely to be explained only by the HIV epidemic.