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Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a leading cause of morbidity and mortality in the Philippines. The purpose of this study was to gain knowledge about the relationship between potential risk factors and MDR-TB. Risk factors (the independent variables) for MDR-TB (the dependent variable) include previous TB treatment, infection with HIV, exposure to patients with drug-susceptible TB/MDR-TB, delays in diagnosis and treatment, employment status, smoking, imprisonment, alcohol abuse, and poor compliance with TB treatment regimens. The study was based on the epidemiological approach to causal inference work. A case-control study design was used wherein a quantitative method was applied in data analysis to assess the strength of the pre-identified possible risk factor(s) association to MDR-TB infection. Data were collected using survey questionnaires that were administered to patients (N = 172) from health centers in Leyte, San Mateo Rizal, and San Lazaro. Hypotheses were tested using chi-square analysis, Fisher's exact test, and an odd ratio. Drug-susceptible TB respondents who smoked on a daily basis were three times more likely (95% CI 1.021-13.341, OR 3.69) to develop an MDR-TB infection than were other respondents. Respondents who did not comply with the anti-TB treatment regimen were nine times more likely (95% CI 2.104-43.059, OR 9.519) to develop an MDR-TB infection than other respondents. Health care providers may be able to use study findings to develop programs to help drug-susceptible TB patients stop smoking and better comply with treatment regimens designed to prevent MDR-TB infection, resulting, potentially, in improved public health outcomes for patients.