Introduction: Despite the world has made efforts, the reduction of acquired immunodefi-ciency syndrome (AIDS) related mortality by giving antiretroviral therapy (ART), still HIV/ AIDS is killing people while they are on ART. However, the current progress and associated factors of mortality among ART-taking patients are hardly available. Therefore, this study was aimed to determine predictors of mortality among HIV-infected adult patients after starting antiretroviral therapy in Harar Hospitals, Harari region, Ethiopia. Methods: A facility-based retrospective cohort study was employed with randomly selected 610 medical records of HIV patients on antiretroviral therapy (ART). Adjusted hazard ratio (AHR) with 95% confidence interval (CI) was used to identify predictors of mortality using multivariate Cox proportional hazard model. Results: Among 610 medical records analyzed with a total of 1410.7 follow-up years, 67 (11%) deaths were found giving an overall mortality rate of 4.75 per 100 person-years. The independent predictor of mortality identified was ambulatory/bedridden functional status (AHR=2.48; 95% CI: 1.43-4.28), taking other than Tenofovir-based regimen (AHR=2.5,95% CI; 1.04-5.94), not taking isoniazid preventive therapy (IPT) (AHR=2.8; 95% CI: 1.61,4.71), hemoglobin <11g/dl (AHR=3.33,95% CI 1.94-5.69), and poor adherence to ART (AHR= 3.62, 95% CI: 1.87-7.0). Conclusion: This study demonstrated that poor ART adherence, not taking IPT, and initiating ART with a non-Tenofovir-based regimen and low hemoglobin count were sig-nificantly associated with the risk of death. For this reason, addressing these all significant predictors is essential to prevent early death.