HIV testing is the gateway to HIV treatment and prevention. HIV self-testing (HIVST) has potential to increase testing; however, the potential population-level impact of HIVST on the HIV epidemic and the best strategies for promoting HIVST are unknown. Our aim is to inform public health approaches for promoting HIVST as part of a comprehensive strategy to reduce HIV incidence.Stochastic network-based HIV transmission models were used to estimate how different HIVST strategies would affect HIV incidence in Seattle and Atlanta over 10 years. We included four types of HIV testers and implemented nine replacement and eleven supplementation strategies for HIVST.Replacement of clinic-based tests with HIVST increased HIV incidence in Seattle and Atlanta. The benefits of supplementary strategies depended on the tester type using HIVST. Targeting non-testers averted the highest number of cases per test. In Seattle 2.2 (95%SI=-77, 100.4) and 4.7 (95%SI=-35.7, 60.1) infections were averted per 1000 HIVST when non-testers used HIVST once or twice per year respectively. In Atlanta the comparable rates were 8.0 (95%SI=-60.3 to 77.7) and 6.7 (95%SI=-37.7, 41.0). Paradoxically, increasing testing among risk-based testers using HIVST increased incidence.The population-level impact of HIVST depends on who is reached with HIVST, how kits are used, and by characteristics of the underlying epidemic and HIV care infrastructure. Targeted HIVST can be an effective component of a comprehensive HIV testing strategy. More work is needed to understand how to identify and target non-testers for self-testing implementation.