Background Human immunodeficiency virus (HIV) infection remains the leading cause of morbidity and mortality throughout the world. Antiretroviral therapy has significantly reduced mortality and improved the life expectancy of HIV-infected patients. WHO developed the "universal test and treat" (UTT) program as a strategy for HIV elimination. Universal "test and treat approach" (UTT) is a program that commends for all populations those diagnosed HIV positive receive early treatment not considering their CD4 count and WHO clinical stage. UTT program was implemented a seven-year. Yet, the effect of this program in terms of patient status was not assessed about the current and previous( CD4 and WHO clinical) approach. Methods Institution-based retrospective cohort study was conducted at Public hospitals in Southern Ethiopia with a total of 802 randomly selected records of ART enrolled adults from March 1, 2013, to February 31, 2020. Data were extracted by using a standardized checklist by trained health professionals, then it was cleaned, entered by epidata version 4.2, and analyzed by STATA version 14. The Cox model was used to estimate survival differences across different study variables. Results A total of 790 patients were followed for 1490.8 person-year (PY) of observation. The overall incidence density rate (IDR) of death in the cohort was 3 per-100-PY. The incidence of death was significantly higher in the CD4-based and WHO stage program than the UTT program. The death among CD4-based and WHO stage programs were 3.7 times higher than the UTT program. The log-rank test and Kaplan–Meier survival curve indicated patients enrolled in the UTT program survived longer than patients enrolled in the CD4-based and WHO clinical stage program (log-rank X2 test = 17.6 p-value = 0.001). WHO clinical stage, functional status, Program of ART, New opportunistic infection, Adherence to ART drugs, and Initiation of IPT were predicted mortality from HIV infection. Conclusion Mortality was significantly reduced in the universal test and treat program. Hence, intervention to further reduce deaths has to focus on early initiation of treatment and strengthening universal test and treat programs.