a b s t r a c t Purpose: Drug-resistant tuberculosis (DRTB) is steadily increasing in Mexico, but little is known of patient risk factors in the MexicoeUnited States border region. This preliminary case-control study included 95 patients with active pulmonary TB with drug susceptibility results attending the José E. González University Hospital in the urban hub of Nuevo Leóndthe Monterrey Metropolitan Area. We report potential social and clinical risk factors of DRTB among this hospital-based sample. Methods: We collected data through face-to-face interviews and medical record reviews from 25 cases with DRTB and 70 drug-sensitive controls. DNA was collected to assess an effect of genetic ancestry on DRTB by using a panel of 291,917 genomic markers. We calculated crude and multivariate logistic regression. Results: After adjusting for potential confounding factors, we found that prior TB treatment (odds ratio, 4.5; 95% confidence interval, 0.9e21.1) and use of crack cocaine (odds ratio, 4.6; 95% confidence interval, 1.1e18.7) were associated with DRTB. No other variables, including genetic ancestry and comorbidities, were predictive. Conclusions: Health care providers may benefit from recognizing predictors of DRTB in regions where routine drug susceptibility testing is limited. Prior TB treatment and illicit drug use, specifically crack cocaine, may be important risk factors for DRTB in this region