The early detection and management of infections is crucial to control epidemics. We evaluated the feasibility and utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen rapid diagnostic tests (Ag-RDTs) for the timely detection of and response to coronavirus disease 2019 in high-risk border communities in Uganda. Between May and September 2022, monthly cross-sectional surveys were conducted in 11 schools and two markets in two border districts. Only baseline and end-line testing were also performed in matched control communities. Antigen rapid diagnostic test results and demographic and clinical data were collected, and contacts of patients were traced and tested. All patients were advised to self-isolate, and compliance was assessed on day 5. We enrolled 10,406 participants out of 10,472 screened individuals. The participants had a 1.3% test positivity rate, with schools recording higher, but non-significant, positivity rates than markets (1.4% versus 0.9%; P = 0.149). We tracked 556 contacts, and 536 (96.4%) agreed to test. The test positivity rate was significantly higher among contacts than the index participants (8.8% versus 1.3%; P <0.001). Only 55 (29.7%) of the index participants self-isolated effectively. Settings that received monthly testing had lower end-line positivity rates than controls (0.3% versus 1.4%; P = 0.001). Repeated SARS-CoV-2 Ag-RDT testing is feasible and could reduce SARS-CoV-2 infections. However, the participation in testing may have been enhanced by the compensation provided. Also, isolation was limited, which may reduce the impact of the intervention when rolled out on a large scale. Innovative strategies to increase the isolation of patients could improve the utility of early testing for transmission reduction during epidemics.