Multi Drug Resistant Tuberculosis (MDR-TB) is a public health challenge, which itself remains a global public health problem. Its impact is worsened by co-infection with Human immunodeficiency virus (HIV). In order to institute successful TB control strategies, factors for development of MDR-TB must be understood. This study aimed to identify and describe clinical and demographic determinants for development of MDR-TB among TB patients. This was a cross sectional, hospital-based studyconducted between April 2017 and December 2019 involving 428 presumptive MDR-TB patients. Specimens were subjected to GeneXpert MTB/RIF assay, microscopy and Line probe assay for diagnosis of MDR-TB. A questionnaire was used to collect demographic information from patients. The odds of having MDR-TB among patients who were cigarette smokers were four-times compared to non-smoking patients (aOR=3.94; 95%CI:1.845-8.428, p<0.001). Alcohol abuse increased the chances of having MDR-TB by ten times (aOR=9.98: 95%CI; 2.414-41.267, p=0.001). Being HIV positive strongly increased the likelihood of having MDR-TB (aOR=2266.0: 95% CI; 407.5-2599.8, p<0.001). Compared to treatment failure, relapse and non-adherence were found to be strong predictors for MDR-TB (aOR=64.22: (95% CI; 12.786-322.507) p=0.001), and (aOR=37.44: (95% CI; 3.895-359.836, p=0.002), respectively.HIV infection, TB relapse, history of irregular treatment, cigarette smoking, alcohol abuse, and treatment failure (return) isfactors development of MDR-TB. Integrated TB/HIV control programs that will include the establishment of strong diagnostic and drug delivery systems, patient management, and TB resistance surveillance systems are recommended.