Aim and objective Although studies have described the clinical profile of patients admitted to the intensive care unit (ICU) with tuberculosis, it is unclear if the type of tuberculosis (pulmonary, extrapulmonary, or disseminated) impacts outcome. Matrials and methods Demographic data, microbiology, treatment, and outcomes over 5 years (2012–16) were obtained from electronic records. Patients were categorized as pulmonary, extrapulmonary, or disseminated tuberculosis. Comparisons were done using t test and Fisher's exact test as appropriate. Predictors of outcome were explored using bivariate and multivariate logistic regression analysis and expressed as odds ratio (OR) with 95% confidence intervals (CI). Results Of the 428 ICU admissions with suspected tuberculosis, 212 (121 male) patients with mean (standard deviation) age of 41.9 (16.7) years and APACHE-II score of 20.8 (6.6) were diagnosed as pulmonary ( n = 55) and extrapulmonary ( n = 52) or disseminated tuberculosis ( n = 105). In 50.5%, the diagnosis of tuberculosis was established during the current ICU admission when they presented with organ dysfunction. Overall, microbiological confirmation was possible in 75.5%; 14 (10.3%) isolates were Rifampicin resistant. ICU admission was required primarily for ventilation ( n = 176; 83%) and hemodynamic instability ( n = 67; 32%). Hospital mortality was 50%. Outcomes were similar in the three groups except for longer duration of stay ( p value = 0.04) in disseminated tuberculosis. On multivariate logistic regression analysis, pulmonary tuberculosis (OR 2.83; 95% CI 1.15–6.95) and vasoactive treatment (OR 15.8; 95% CI 6.4–39.2) were independently associated with death; need for ventilation predicted mortality perfectly. Conclusion In this cohort of patients admitted to ICU with tuberculosis, 50% were newly diagnosed during ICU admission. Pulmonary site of involvement and need for organ support are independent risk factors for death. How to cite this article Thomas L, Chacko B, Jupudi S, Mathuram A, George T, Gunasekaran K, et al. Clinical Profile and Outcome of Critically Ill Patients with Tuberculosis. Indian J Crit Care Med 2021;25(1):21–28.