Background: Acquired Immune deficiency syndrome is an infectious diseases caused by human immunodeficiency virus (HIV) which primarily targets an individual's immune system. In Ethiopia, nearly 24% of HIV-related deaths occur in children under the age of five; however studies regarding survival time of HIV-positive under five children after anti-retroviral therapy initiation are limited with poor evidence of predictors of death. Objective: To assess survival time and predictors of death among HIV infected under five children after initiation of anti-retroviral therapy in West Amhara Referral Hospitals, Northwest Ethiopia, 2021. Methods: A multicenter institution based retrospective follow up study was conducted in 432 HIV-positive under five children on anti-retroviral therapy selected by simple random sampling from January 2010 to December 2019. A standardized data extraction tool was employed which was adapted from anti-retroviral therapy entry and follow-up forms. The event of interest for this study is death whereas absence of experience of death is censored. Data was entered into Epi- Data version 3.1 then export to STATA version 14. Kaplan Meier curve was used to estimate the survival probability. Cox regression model was used to identify independent predictors of death. Result:-Among 415 records included in the final analysis, 25(6.02%) of the individuals were died. The incidence rate of death was found to be 2.87 per 1000 child-months (95%CI: 1.94 - 4.25). The cumulative survival probabilities of children after 6, 12, 24, and 36 months were 0.97, 0.95, 0.92 and 0.85 respectively. HIV-infected under-five children who lived in rural area (AHR 3.32:-95% CI 1.17- 9.39), with poor adherence to anti-retroviral therapy (AHR=3.36; CI: 1.06, 10.69), without Isoniazide prophylaxis (AHR=3.15; CI: 1.11, 8.94) and with anemia (AHR: 3.05, 95% CI: 1.16, 8.03) were at higher risk of death. Conclusion and recommendation:-Death of HIV-infected under-five children on anti-retroviral therapy is high within the first one year after enrolment. The risk of death was higher for those who are rural resident, had poor adherence, lack Isoniazide prophylaxis and present with anemia. Therefore, clinicians shall emphasize for those lived in rural area, Isoniazide prophylaxis, present with poor adherence, anemia and in early phase of anti-retroviral therapy. Key words: Anti-Retroviral Therapy, Under-Five Children,