© 2020 Ahmed A. Hassan, Zainab Taha, Mohammed A. Abdulla, AbdelAziem A. Ali, Ishag Adam. BACKGROUND: According to the World Health Organization estimation, African Region deaths of all under-five deaths in 2015 were over 5 times higher in comparison to the European Region. AIM: The study aimed to estimate the prevalence, investigate the possible causes and risk factors associated with under-five children’s hospitalization in Kassala, Eastern Sudan. METHODS: A community-based cross-sectional study was conducted from December 2015 to March 2016. The data were collected by interviewing mothers. RESULTS: A total of 297 mother-child pairs participated in the study. The mean (SD) of maternal age and children’s age was 27.6 (5.9) years and 16 (11.3) months, respectively. One hundred and three children were hospitalized over the past 6 months. The most common mentioned causes for the last hospitalization were gastroenteritis 28.1% (29/103), respiratory tract infections 19.4% (20/103), malaria 9.7% (10/103), and trauma 3.8% (3/103). In multivariable analysis, a high birth order (adjusted odds ratio [AOR] 1.25, 95% Confidence Interval [CI] (1.06, 1.47), low paternal education (AOR 2.89, 95% 1.32, 6.30), and bottle feeding (AOR 2.26, 95% CI 1.30, 3.80) were associated with under-five children’s hospitalization. CONCLUSIONS: More than one-third of the children were hospitalized in Eastern Sudan. Urgent action is required to address children’s health issues (i.e., the above-mentioned causes and associated factors).