Background: Treating patients with multidrug-resistant tuberculosis (MDR-TB) strains is more complicated, complex, toxic, expensive, than treating patients with susceptible TB strains. This study aims to compare the treatment outcomes and potential factors associated between patients with MDR-TB and non MDR TB infections in peninsular Malaysia. Methods: This study was a retrospective cohort study. Data were collected from the medical records of all registered MDR-TB patients and Non-MDR-TB patients at five TB hospitals in peninsular Malaysia from January 2010 to January 2014. Results: A total of 314 subjects were studied, including 105 MDR-TB cases and 209 non-MDRTB. After TB treatment, 24.8% of the MDR-TB patients and 17.7% of non MDR TB relapsed; 17.1% of the MDR-TB patients and 16.3% of non MDR TB defaulted from TB treatment. A significant difference seen in treatment success rate 17.1% for MDR-TB; 63.1% for non MDR TB (P < 0.001)). Mortality rate were 8.9% for MDR-TB; 13.2% for non MDR TB. Multivariable analysis showed the potential factors associated with poor treatment outcomes were presence of HIV infection (AOR, 1.09; 95%CI: 1.05, 1.75; P = 0.001) and previous TB treatment (AOR, 4.87; 95%CI: 2.84, 8.38; P = 0.001). Conclusion: This study revealed that the treatment success rate in patients with non MDR TB infection was higher than MDR-TB. Unsuccessful treatment was seen in MDR-TB associated with potential factors such as history of TB treatment, and presence of HIV infection.