Background <p>Children living with HIV continue to face high mortality rates in resource-limited settings, especially in sub-Saharan Africa. In Angola, there is a lack of robust data to guide clinical and programmatic strategies targeting this vulnerable population. This study aimed to estimate survival and identify predictors of mortality in children with HIV followed up at a paediatric referral hospital in Angola.</p> Methods <p>A retrospective cohort study of children (≤ 15 years) who started ART between 2016 and 2018, with follow-up until 2023. Kaplan–Meier curves and Cox regression models were used to estimate survival and identify factors associated with death.</p> Results <p>During 1,577 person-years of follow-up, a total of 420 deaths occurred, corresponding to a mortality rate of 26.6 deaths per 100 person-years. The median follow-up time was 11.9 months (interquartile range: 3.4–38.5). Median survival was significantly lower among children with non-vertical transmission, WHO clinical stage III/IV, CD4 counts below the age-specific threshold, underweight status, and opportunistic infections. In the multivariable Cox model including transmission route, WHO clinical stage, baseline CD4 count, underweight status, and age group, non-vertical transmission (AHR 1.35, 95% CI 1.11–1.65), WHO clinical stage III/IV (AHR 1.82, 95% CI 1.36–2.46), and CD4 below the age-specific threshold (AHR 1.82, 95% CI 1.06–3.12) remained independent predictors of mortality.</p> Conclusion <p>The high mortality observed in this cohort was associated with advanced clinical severity at admission. The finding that non-vertical transmission was independently associated with mortality suggests the need for improved screening and tailored care strategies for children and adolescents infected outside the mother-to-child context. Strengthening early diagnosis and timely initiation of ART is crucial to reducing preventable deaths and achieving global paediatric HIV control targets.</p>