Human tuberculosis is still a major world health concern. In Uruguay, contrary to the world trend, an increase in cases has been observed since 2006. Although the incidence of MDR-resistant strains is low and no cases of XDR-TB were registered, an increase in the number of patients with severe tuberculosis requiring critical care admission was observed. As a first aim, we performed the analysis of the genetic structure of strains isolated from patients with severe tuberculosis admitted to an intensive care unit. We compared these results with those corresponding to the general population observing a statistically significant increase in the Haarlem genotypes among ICU patients (53.3% vs 34.7%; p < 0.05). In addition, we investigated the association of clinical outcomes with the genotype observing a major incidence of hepatic dysfunctions among patients infected with the Haarlem strain (p < 0.05). The cohort presented is one of the largest studied series of critically ill patients with tuberculosis.