BackgroundGlobally, childhood diarrhea is amongst the most prevalent health problems and accounts for 9% of all deaths in children under-five. In Ethiopia, childhood diarrhea is a major public health problem in which the prevalence ranges from 13.5 to 30.5% and experienced by multiple factors. Although health extension program has been implementing for couples of years; diarrheal disease remains the second cause of morbidity and continues an important public health problem in the study district. Thus, this study assessed determinants of diarrheal disease among under-five children in the Medebay Zana district, northwest Tigray, Ethiopia, 2015.MethodA community based case-control study was used. A multistage sampling procedure was employed to enroll the study participants. Data were collected using face to face administered questionnaire. The collected data were entered into Epi Info version 3.5.4 and exported to SPSS Version 21 for analysis. Frequencies with percentages were computed using univariate analysis. Finally, logistic regression model was fitted to identify factors associated with childhood diarrhea where P-values of less than 0.05 were considered statistically significant.ResultsSocio-demographic factors such as low maternal educational level [AOR = 2.88, 95% CI (1.70, 4.88)], being index child of older age, households with ≥3 number of children under-five [AOR = 4.05, 95% CI (1.91, 8.60)] and maternal history of diarrhea [AOR = 2.10, 95% CI (1.09, 4.05)] were statistically associated with childhood diarrhea. This study also revealed that child feeding practice; not exclusively breastfed [AOR = 4.84, 95% CI (2.21, 10.60)] and initiation of complementary feeding above 6 months [AOR = 1.78, 95% CI (1.09, 2.92)] were statistically associated with outcome variable. Environmental and behavioral practices such as unavailability toilet facility [AOR = 2.10, 95% CI (1.34, 3.30)], improper solid waste disposal [AOR = 2.29, 95% CI (1.53, 3.44)] and unprotected drinking water [AOR = 1.83, 95% CI (1.12, 2.98)] were also found significant factors of childhood diarrhea.ConclusionMaternal educational status, age of index child, number of < 5 children, child feeding practices, maternal history of diarrhea, toilet facility, solid waste disposal and household drinking water were found determinants of childhood diarrhea. These findings have policy implications and insight the strengthening for health intervention programs.