Indonesia ranked 6th from countries with the highest burden of drug-resistant pulmonary tuberculosis (PTB). A rate of 1.9% of new cases develop to be resistant and even 12% from previous treated cases. Previous studies concluded determinants of drug-resistant PTB, however, the study in Indonesia, especially in the scope of hospitals is still limited. Our study aims to explore the determinant of drug-resistant PTB in Dr. Kariadi General Hospital. We conducted a case-control study, using data from medical records. A sample of 76 cases and 76 controls have met the criterion and were involved in the study. The status of drug-resistant cases determined by rapid molecular test. We observed the subject's characteristics and determinants of drug-resistant PTB. Study shows that there is no significant difference in the subject's characteristics, i.e. age, sex, level of education, and working status between the group of cases and controls. Chi-square analysis shows that history of previous treatment, HIV infection, drug side-effects status, Acid-Fast Bacilli (AFB) gradation, and duration of treatment were related to drug-resistant pulmonary TB. After conducted Binary Logistic Regression, we concluded that history of treatment (OR=24.3; 95%CI: 8.49-69.33) and AFB gradation (OR=13.8; 95% CI: 2.76-68.60) altogether as dominant determinants of drug-resistant PTB.