Background: Human immune deficiency virus (HIV) remains the leading cause of morbidity and mortality globally. It can lead to AIDS, which results in gradual deterioration and failure of the immune system. As the immune system becomes compromised, the patient becomes highly susceptible to life-threatening infection which ends with early death. Even though antiretroviral therapy (ART) significantly decreases mortality as a whole, the rate of death is still the highest, especially in the first and second years of ART initiation. Objectives: To assess the survival and predictors of mortality among HIV-infected adults after initiation of anti-retroviral therapy in Jigjiga Governmental Hospitals, Eastern Ethiopia. Method: Institution-based Retrospective follow-up study was employed among ART patients from January 1, 2015, to December 31, 2021. Data were cleaned and entered in Epi-data version 3.1 and exported to STATA 14 for further analysis. Kaplan–Meier and Log-Rank tests were applied to compare survival differences among categories of different variables. In bi-variable analysis, p-values < 0.20 were included in a multivariable analysis. A multivariate Cox regression model was used to measure the risk of death & identify the significant predictors of death. Variables that p-value < 0.05 were considered statistically significant predictors of mortality. Result in this study 466(53.34%) participants were male and 552(65.56 %) were urban residents about 91(10.81%) have died with an overall incidence rate of 3.92 (95% CI (2.4–5.4)) per 100-person year of observation. The overall survival probability of the study group was 83.97%. In the multivariable Cox regression analysis, baseline WHO stage III/IV (AHR=2.42(1.43-4.09)) have no caregiver (AHR=2.23; 95% CI (1.16-4.29)), being bedridden functional status (AHR=2.18; 95% CI (1.01-4.72)), and poor last known adherence level (AHR=4.23; 95%CI (2.39-7.47)) were found to be significant predictors of mortality. Conclusion: the incidence of death was relatively high, especially in the second year of ART start. Baseline clinical WHO stage Ⅲ/Ⅳ, bedridden functional status at enrolment, and absence of caregiver, poor level of recent adherence was found to be independent predictors of mortality. Patients with these risk factors need special attention and are crucial to reducing the rate of mortality.