Background Diarrheal disease is the second leading causes of death among under-five children. Most of the death due to diarrhea is reporting in developing countries. To prevent this highly prevalent problem, identifying the contributing factors across different settings is necessary. Therefore, this study aimed to identify the determinants of acute diarrhea among under-five children in the Northeast part of Ethiopia. Methods An institution-based unmatched case–control study was conducted among 306 under-five children from March to April 2019. A systematic random sampling technique was employed to select study participants. Data were collected by face to face interviews using a pretested structured questionnaire. Data were entered using Epi-info 7 and analyzed with SPSS version 20.0. We applied logistic regression analysis. Those variables with p-value <0.05 were significant determinants of acute diarrhea. Results Improper child’s stool disposal [AOR=4.12; 95% CI (1.25,13.5)], absence of home-based water treatment [AOR=2.85; 95% CI (1.27,6.42)], did not wash hand at critical times [AOR=5.47; 95% CI (1.68,17.8)], did not practice exclusive breastfeed [AOR=3.32; 95% CI (1.21,9.14], unable to get counseling from health professionals [AOR= 3.23; 95%,CI (1.15,13.5)], provide left over food to the child [AOR=2.96; 95% CI (1.19,7.32)], and maternal diarrhea [AOR=6.06; 95% CI (2.42,15.22)] were determinants of acute diarrhea among under five children. Conclusion Most of the determinants of acute diarrhea could be preventable. Thus, collaborative intervention by emphasizing health education about the importance of personal and environmental hygiene, safe food handling, exclusive breastfeeding practice, and home-based water treatment are essential.

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