Abstract Background: Multidrug-resistant tuberculosis is tuberculosis due to resistance of M. tuberculosis to at least isoniazid and rifampicin. In spite of increased testing, the number of MDR-TB cases detected in 2016 reached 153 000, a slight increase from 2015. The two reasons why MDR-TB continues to emerge and spread are mismanagement of tuberculosis (TB) treatment and person to person transmission. To reduce the burden of MDR-TB, Ethiopia has designed a strategy to provide treatment and culture and drug susceptibility testing (DST) services at least to all MDR-TB suspected cases. However, there are limited data on the determinants of treatment outcome of MDR-TB in the country to guide the National TB Program. Objective: To identify the determinants of treatment outcome of MDR-TB in St. Peter Specialized Hospital, Addis Ababa Ethiopia Methods: An institution based unmatched case control study design was employed on MDR-TB patients. A total of 354 (71 case and 283 controls) MDR-TB treated patients between 2010 and 2018 were included. Patients were selected by simple random sampling method. Data were extracted from patients’ MDR-TB registration books and medical records. A Binary Logistic regression analysis was performed; bi-variable logistic regression was employed to identify candidate variables for multivariable logistic regression at P< 0.2. Factors associated with treatment outcome of MDR-TB was identified in multivariable logistic regression at P<0.05 and odds ratio with 95% CI. Model was diagnosed by Hosmer - Lemeshow goodness of fit test with a P value of 0.68; it shows that the model was well fit for the data in this study. Results: In the multivariable logistic regression, individuals with a history of taken second line drug were 4.465 times [95% CI: 2.141-9.312] more likely to have poor treatment outcomes. And also individual with more than two first line TB drug resistant were 3.092 times [95% CI: 1.092 - 8.696] more likely to have poor treatment outcome. The study also revealed that individuals with a history of developing adverse effect on the course of treatment were 6.305 times [95% CI: 1.536-25.881] more likely to have poor treatment outcome. In addition individuals with primary education were 77.7 % (OR=0.223 [95% CI: 0.104-0.489]) less likely to have poor treatment outcome and patients with low hemoglobin level were also 52.5 % (OR=0.475 [95 % CI: 0.227-0.996]) less likely to have poor treatment outcome. Conclusion and Recommendation: This study concluded that patients with a history of taken second line TB drugs, developing adverse effect on the course of treatment, and resistance of more than two first lines TB drugs at the commencement of treatment are important determining factor for treatment outcome. Thus, this study urges that hospitals should strengthen follow up system for a patients with adverse effect, history of taken second line TB drug and resistance of more than two MDR TB drugs. Keywords: MDR-TB, treatment outcome, determinants