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Background: Diarrheal diseases, are major concerns for Ugandan children; persistent in Obongi District despite high rotavirus vaccination rates (2019-2021). The district recorded the country's highest annual acute watery diarrhea (AWD) incidence from 2017 to 2021. Our study, conducted in April 2022, assessed AWD risk factors among 0-59-month-old children in Obongi., Methods: We conducted a 1:2 (193:386) unmatched case-control study. A case was a child (0-59 months) with ≥ 3 loose/liquid stools/day, negative malaria/pneumonia tests, residing in Itula/Parolinya subcounty from 1 to 30 April 2022. Medical records from 10 facilities were reviewed. Simple random sampling identified cases, who were interviewed, and controls were randomly chosen from non-AWD neighboring households. Child health cards provided vaccination details. We used logistic regression to identify factors associated with AWD., Results: Among 193 cases and 386 controls, 104 (54 %) cases and 183 (47 %) controls were male, 58 (30 %) cases and 127 (33 %) controls were aged 12-23 months, 187 (97 %) cases and 369 (96 %) controls had received at least one dose of rotavirus vaccine, 58 (30 %) cases and 120 (34 %) controls treated drinking water. Comorbidity presence (undernutrition, diabetes, HIV) (AOR = 12; CI: 2.5-53), caregiver's unwashed hands post-toilet (AOR = 3.9; CI: 1.2-13), and borehole vs. piped water (AOR = 4.0; CI: 1.7-9.6) linked to AWD., Conclusion: Modifiable factors, including failure of caregivers to wash their hands with soap after visiting toilets and use of borehole water were associated with AWD, suggesting that community sensitization on handwashing at critical times, using clean water and soap, and expanded use of piped water could reduce AWD incidence in this area., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)