Background: Tuberculosis remains a major global health problem and ranks along with the human immunodeficiency virus (HIV) as a leading cause of mortality worldwide. The aim of this study was to investigate the treatment outcome of tuberculosis, and factors associated with treatment outcome of tuberculosis in TB patients enrolled in Arsi-Robe Hospital, Oromia regional state, South eastern Ethiopia between January 2013 to December 2017. Methods: An Institutional-based retrospective study was conducted in Arsi-Robe Hospital from 2013 to 2017 in study patients who had all forms of TB in DOTS clinic. The predictors of treatment outcomes were analyzed through bivariate and multivariable logistic regression analysis and a P-value < 0.05 were considered statistically significant. Results: Out of the 257 registered TB patients, most of them were males (57.9%), from rural areas (62.6%) and in age of 15-24 category (39.3%). PTB-, PTB+ and EPTB were recorded in 48.2%, 32% and 19.8% of the patients, respectively. Among all cases, 8.6% had TB-HIV co-infection. Among all TB cases, 84.0% had successful treatment outcome. TB patients from urban areas (AOR: 3.34, 95% CI: 1.338.38, P = 0.01), with failure treatment (AOR: 6.66, 95% CI = 1.12- 39.57; P = 0.037) and HIV positive (AOR: 4.92, 95% CI = 1.38-17.51; P = 0.014) had higher odd of unsuccessful treatment outcome of tuberculosis. However, TB patients with PTB+ (AOR: 0.1470, 95% CI = 0.031-0.687; P = 0.015) and EPTB (AOR: 0.194, 95% CI = 0.054-0.688; P = 0.011) had significantly lesser odd of unsuccessful treatment outcome. Conclusions: Being urban resident, treatment failure and HIV positive considerably challenge the treatment outcome of tuberculosis, but being PTB+ and EPTB were associated with higher treatment success rate of TB. Continuous follow-up of patients with unsuccessful treatment outcome of tuberculosis with strengthened implementation of the DOTs strategies are suggested. Trial Registered: retrospectively registered