Background Multi-drug resistant Tuberculosis (MDR-TB) is a strain of Mycobacterium tuberculosis that is resistant to at least Rifampicin and Isoniazid drugs. The treatment success rate for MDR-TB cases is lower than for drug susceptible TB. Globally only 55% of MDR-TB patients were successfully treated. Monitoring the early treatment outcome and better understanding of the specific reasons for early unfavorable and unknown treatment outcome is crucial for preventing the emergence of further drug-resistant tuberculosis. However, this information is scarce in Ethiopia. Therefore, this study aimed to determine the intensive phase treatment outcome and contributing factors among patients treated for MDR-TB in Ethiopia. Methods A 6 year retrospective cohort record review was conducted in fourteen TICs all over the country. The records of 751 MDR-TB patients were randomly selected using simple random sampling technique. Data were collected using a pre-tested and structured checklist. Multivariable multinomial logistic regression was undertaken to identify the contributing factors. Results At the end of the intensive phase, 17.3% of MDR-TB patients had an unfavorable treatment outcome, while 16.8% had an unknown outcome with the remaining having a favorable outcome. The median duration of the intensive phase was 9.0 months (IQR 8.04–10.54). Having an unfavorable intensive phase treatment outcome was found significantly more common among older age [ARRR = 1.047, 95% CI (1.024, 1.072)] and those with a history of hypokalemia [ARRR = 0.512, 95% CI (0.280, 0.939)]. Having an unknown intensive phase treatment outcome was found to be more common among those treated under the ambulatory care [ARRR = 3.2, 95% CI (1.6, 6.2)], rural dwellers [ARRR = 0.370, 95% CI (0.199, 0.66)], those without a treatment supporter [ARRR = 0.022, 95% CI (0.002, 0.231)], and those with resistance to a limited number of drugs. Conclusion We observed a higher rate of unfavorable and unknown treatment outcome in this study. To improve favorable treatment outcome more emphasis should be given to conducting all scheduled laboratory monitoring tests, assignment of treatment supporters for each patient and ensuring complete recording and reporting which could be enhanced by quarterly cohort review. Older aged and rural patients need special attention. Furthermore, the sample referral network should be strengthened.