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Background: An extensive literature supports expanded HIV screening in the United States. However, the question of whom to test and how frequently remains controversial. Objective: To inform the design of HIV screening programs by identifying combinations of screening frequency and HIV prevalence and incidence at which screening is cost-effective. Design: Cost-effectiveness analysis linking simulation models of HIV screening to published reports of HIV transmission risk, with and without antiretroviral therapy. Data Sources: Published randomized trials, observational cohorts, national cost and service utilization surveys, the Red Book, and previous modeling results. Target Population: US communities with low to moderate HIV prevalence (0.05% to 1.0%) and annual incidence (0.0084% to 0.12%). Time Horizon: Lifetime. Perspective: Societal. Interventions: One-time and increasingly frequent voluntary HIV …