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Background: In June 2019, surveillance data from the Uganda's District Health Information System revealed an outbreak of malaria in Kole District. Analysis revealed that cases had exceeded the outbreak threshold from January 2019. The Ministry of Health deployed our team to investigate the areas and people affected, identify risk factors for disease transmission, and recommend control and prevention measures., Methods: We conducted an outbreak investigation involving a matched case-control study. We defined a confirmed case as a positive malaria test in a resident of Aboke, Akalo, Alito, and Bala sub-counties of Kole District January-June 2019. We identified cases by reviewing outpatient health records. Exposures were assessed in a 1:1 matched case-control study (n = 282) in Aboke sub-county. We selected cases systematically from 10 villages using probability proportionate to size and identified age- and village-matched controls. We conducted entomological and environmental assessments to identify mosquito breeding sites. We plotted epidemic curves and overlaid rainfall, and indoor residual spraying (IRS). Case-control exposures were combined into: breeding site near house, proximity to swamp and breeding site, and proximity to swamp; these were compared to no exposure in a logistic regression analysis., Results: Of 18,737 confirmed case-patients (AR = 68/1,000), Aboke sub-county residents (AR = 180/1,000), children < 5 years (AR = 94/1,000), and females (AR = 90/1,000) were most affected. Longitudinal analysis of surveillance data showed decline in cases after an IRS campaign in 2017 but an increase after IRS cessation in 2018-2019. Overlay of rainfall and case data showed two malaria upsurges during 2019, occurring 35-42 days after rainfall increases. Among 141 case-patients and 141 controls, the combination of having mosquito breeding sites near the house and proximity to swamps increased the odds of malaria 6-fold (OR = 6.6, 95% CI = 2.24-19.7) compared to no exposures. Among 84 abandoned containers found near case-patients' and controls' houses, 14 (17%) had mosquito larvae. Adult Anopheles mosquitoes, larvae, pupae, and pupal exuviae were identified near affected houses., Conclusion: Stagnant water formed by increased rainfall likely provided increased breeding sites that drove this outbreak. Cessation of IRS preceded the malaria upsurges. We recommend re-introduction of IRS and removal of mosquito breeding sites in Kole District., (© 2022. The Author(s).)