Introduction: Acquired immune deficiency syndrome (AIDS) is a medical condition caused by hu-man immunodeficiency virus (HIV), and has been the major concern worldwide. Despite antiretroviral treatment (ART) has shown significant clinical importance by meeting the goal of the rapy, there is still a number of deaths due to socio-economic, demographic, and health-related factors. Therefore, this study was aimed to investigate the survival status and predictors of mortality for adult HIV-positive patients treated with ART. Material and methods: A retrospective cohort study was conducted with 1,285 of HIV-infected patients aged 15 years and greater, who were enrolled in ART at Mizan-Tepi University Teaching Hospital from September, 2007 to January, 2015. A multivariable Cox regression model was applied to assess significant predictors of mortality. Results: During follow-up period, a total of 1,285 patients contributed to 59,237 person-year of follow-up, and 273 (21%) of the patients died, showing overall incidence rate of 4.6 per 1,000 person-year (273/59,237). The median follow-up period was 44 months. During follow-up, 273 (21%) pa-tients died, of whom nearly 32% and 12% of deaths occurred within 6 months and between 6 and 12 months of highly active antiretroviral therapy (HAART) initiation, respectively. Conclusions: Multivariable Cox proportional hazards model revealed that having concomitant tu-berculosis infection, low baseline CD4 count, low baseline weight, living in rural area, using of a sub-stance, older age, lower educational level, higher World Health Organization (WHO) clinical stages, functional status, and marital status were all significantly associated with progression to death for HIV/AIDS-infected patients.