摘要:Even though the global under-five mortality rate substantially decreased over time, Sub-Saharan African (SSA) countries including Ethiopia continue to share the huge burden of under-five mortality. Ethiopia showed a substantial reduction in under-five mortality over time but the rate of reduction has varied across regions. Therefore, this study aimed to investigate determinants of under-five mortality in the high mortality regions of Ethiopia. A secondary data analysis was done based on the 2016 Ethiopian Demographic and Health Survey (EDHS) data. A total weighted sample of 3446 live births were included for this study. For the determinants of under-five mortality, mixed-effect logistic regression was fitted. The Intra-Class Correlation Coefficient (ICC), and Median Odds Ratio (MOR) were done to assess the presence of a significant clustering effect. The standard binary logistic regression and the mixed-effect logistic regression model were fitted and deviance (−2LL) was used for model comparison as the models were nested models. Variables with a p-value less than 0.2 in the bi-variable mixed-effect binary logistic regression analysis were considered for the multivariable analysis. In the multivariable mixed-effect logistic regression analysis, the Adjusted Odds Ratio (AOR) with the 95% Confidence Interval (CI) were reported to declare the statistical significance and strength of association of under-five mortality and the determinant factors. Overall, the under-five mortality rate in the high mortality regions of Ethiopia was 74 per 1000 live births and it was highest among twin births (262 per 1000 live births). In the multivariable mixed-effect logistic regression analysis, being having 6 and above births (AOR = 3.66, 95% CI: 1.55, 8.67), preceding birth interval of 2–3 years (AOR = 0.57, 95% CI: 0.41, 0.81) and above 3 years (AOR = 0.35, 95% CI: 0.22, 0.55), being twin (AOR = 5.12, 95% CI: 2.28, 11.46), and being having antenatal care (ANC) visit during pregnancy (AOR = 0.27, 95% CI: 0.16, 0.45) were significant determinants of under-five mortality. In this study, under-five mortality rate was highest in high mortality regions of Ethiopia. Parity, ANC visit, preceding birth interval, and multiple births were significant predictors of under-five mortality. Therefore, public health interventions that increase maternal health service utilization such as ANC and family planning service utilization to increase birth interval are needed to reduce under-five mortality among these regions of Ethiopia.