<p>Indoor Residual Spraying (IRS) is the application of a long-lasting residual insecticide to indoor household surfaces to control malaria. During 2016-2020, Uganda used Actellic and Sumishield insecticides for IRS. In 2021, to limit insecticide resistance, Fludora Fusion was introduced as a new IRS chemical for 85% of IRS households. However, four of 14 sprayed districts had malaria upsurges immediately after IRS. We evaluated the impact of IRS in these districts and investigated possible factors contributing to less effective IRS in 2021.</p>