Abstract: A matched case-control study was conducted to identify the factors associated with MDR in the Upper Northeast Thailand. The ratio of MDR per non-MDR was 1:2 and medical records were retrospectively reviewed. To identify the factors associated with MDR by conditional logistic regression analysis and were presented by adjusted matched Odds Ratio (mORadj) and 95% confidence interval (95% CI). In total 273 cases were included, divided into 91 MDR and 182 non-MDR. The factors associated with MDR; irregular TB follow up in the past was 264.6 times higher risk (95% CI: 23.1-3036.4) to have MDR. DOT by self administrative was 36.0 times higher risk (95% CI: 2.3-576.2) as compared with DOT by health care providers. Co-morbidity diseases were 5.8 times higher risk to have MDR (95% CI: 1.5-21.9). Strengthening DOTs strategy for shorting the delay of diagnosis and treatment, decreasing irregular TB follow up that aimed to increase success rate and prevent MDR. Should be developed TB/DM collaborative strategies and guidelines for preventing the transmission of M. tuberculosis in DM patients.