Molecular typing techniques make it possible to genetically characterize Mycobacterium tuberculosis isolates. Public health strategies to control the spread of tuberculosis are enhanced by the use of molecular data to study tuberculosis transmission dynamics within populations. This study compared epidemiological and clinical characteristics of three M. tuberculosis groups based on polymorphisms at katG codon 463 and gyrA codon 95 in 1893 culture-positive patients by a retrospective nested case-comparison design. Study participants, diagnosed from 1995 to 2001 in the Houston, Texas metropolitan area, were >/= 18 years old, 70% male, 66% U.S.-born, 40% Black, 29% Hispanic, 19% White, and 12% Asian/Pacific Islander. The prevalence of each principal genetic group (GG) was 30% (GG1), 52% (GG2), and 18% (GG3). Multiple logistic regression analysis showed that GG1 participants were more likely to be Asian, male, and have a history of homelessness, as compared with participants with either GG2 or GG3 isolates. GG2 participants were more likely to be Hispanic, have streptomycin-resistant isolates, and be infected with HIV than either GG1 or GG3 participants. GG3 participants were more likely to be Black or Hispanic, report illicit drug use, and live in a congregative facility at the time of diagnosis, than GG1 or GG2 participants. Ethnicity and sociodemographic findings were significant, prompting additional research into social networks, genetic susceptibility, immunology, and virulence factors.