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Tracheostomy is frequently performed in critically ill patients requiring prolonged mechanical ventilation, but evidence regarding its prognostic impact in infectious diseases remains limited. This retrospective cohort study analyzed 607 patients who underwent tracheostomy at a specialized infectious disease hospital in Brazil between May 2020 and April 2025. Demographic data, comorbidities, severity scores, perioperative variables, and clinical outcomes were extracted from medical records, and multivariate logistic regression identified factors independently associated with in-hospital mortality. Overall hospital mortality was 64.6%. Age over 60 years, diabetes mellitus, higher SAPS 3 score, coagulopathy, need for hemodialysis, and a PaO₂/FiO₂ ratio below 200 on the day of tracheostomy were independently associated with death. In a sensitivity analysis excluding patients with COVID-19, HIV infection (analyzed as an underlying comorbidity) was associated with increased mortality, while the use of combined antiretroviral therapy was associated with improved survival; these results should be interpreted as exploratory. Overall, outcomes after tracheostomy in patients with infectious diseases appear to be driven primarily by systemic severity and organ dysfunction rather than by infectious etiology, underscoring the importance of individualized, multiparametric prognostic assessment.