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Objectives: Our objective was to describe and determine the factors contributing to a recent drug-resistant tuberculosis (TB) outbreak in Georgia. Methods: We defined an outbreak case as TB diagnosed from March 2008 through December 2015 in a person residing in Georgia at the time of diagnosis and for whom (1) the genotype of the Mycobacterium tuberculosis isolate was consistent with the outbreak strain or (2) TB was diagnosed clinically without a genotyped isolate available and connections were established to another outbreak-associated patient. To determine factors contributing to transmission, we interviewed patients and reviewed health records, homeless facility overnight rosters, and local jail booking records. We also assessed infection control measures in the 6 homeless facilities involved in the outbreak. Results: Of 110 outbreak cases in Georgia, 86 (78%) were culture confirmed and isoniazid resistant, 41 (37%) occurred in people with human immunodeficiency virus coinfection (8 of whom were receiving antiretroviral treatment at the time of TB diagnosis), and 10 (9%) resulted in TB-related deaths. All but 8 outbreak-associated patients had stayed overnight or volunteered extensively in a homeless facility; all these facilities lacked infection control measures. At least 9 and up to 36 TB cases outside Georgia could be linked to this outbreak. Conclusions: This article highlights the ongoing potential for long-lasting and far-reaching TB outbreaks, particularly among populations with untreated human immunodeficiency virus infection, mental illness, substance abuse, and homelessness. To prevent and control TB outbreaks, health departments should work with overnight homeless facilities to implement infection control measures and maintain searchable overnight rosters.