The association between tuberculosis (TB) and diabetes is re-emerging with the epidemic of type 2 diabetes (T2DM). We analyzed retrospective data from 2878 TB patients across the Texas/Mexico border. Overall, 161/2878 (5.6%) patients had MDR TB (resistance to rifampin and isoniazid): Texas 49/1442 (3.4%) and Mexico 112/1436 (7.8%). In Texas, MDR TB was significantly associated with T2DM (OR 2.1, 95% CI 1.1-4.2) when adjusted for age, gender, drug and alcohol abuse, HIV infection and history of previous episode of TB; and in Mexico (OR 1.80, 95% CI 1.1-2.9) when adjusted for age and gender. Patients with T2DM in both countries were more likely to be compliant with DOTS therapy (Texas: OR 2.4, 95% CI 1.1-5.4) than patients without T2DM. In Texas, all but 3 of the T2DM patients with MDR TB were resistant at their first culture at the time of diagnosis. It is possible that impaired immunity in T2DM increases susceptibility to infection with resistant strains.