BACKGROUND The Centers for Disease Control and Prevention (CDC) estimates that 3.2 million Americans are living with chronic hepatitis C virus (HCV) infection and 50%-70% are unaware of their status. Although therapies are available that can suppress or eliminate infection, identifying persons infected with HCV is challenging. Rapid tests could help identify many of these persons more expeditiously. METHODS Three manufacturers, Chembio, OraSure, and MedMira, submitted HCV antibody (anti-HCV) rapid screening assays to the CDC for evaluation and comparison with established anti-HCV screening assays. The panel consisted of 1100 specimens drawn during 1997-1999 from persons reporting injection drug use. Sensitivity and specificity were assessed using 2 reference approaches, one based on the reactivity of samples in an anti-HCV screening assay and the other based on CDC HCV testing algorithm. RESULTS The sensitivities of the Chembio, MedMira, and OraSure assays across the 2 approaches were 96.2%-98.0%, 86.8%-88.3%, and 97.8%-99.3%, respectively. The 3 assays had specificity of 99.5% or higher with no differences between assays. False rapid assay results were associated with human immunodeficiency virus positivity for both approaches for Chembio and MedMira. CONCLUSIONS Rapid anti-HCV tests can provide sensitive and specific anti-HCV results for high-risk patients.