The new Cobas Core Anti-HCV EIA was evaluated in two centers for its ability to detect antibodies directed to hepatitis C virus in human serum. This assay, which can be run fully automated on a random access analyzer, was compared with three other commercially available screening tests: the Ortho HCV 3.0 ELISA, the Murex anti-HCV, and the Abbott HCV EIA second generation. Positive or discrepant results were further investigated using the Wellcozyme HCV Western Blot or the Abbott Matrix HCV assays. The results obtained from analyzing 5045 serum samples showed a high correlation between the Cobas Core Anti-HCV EIA and the other screening assays, ranging from 98.9% to 99.9%. Diagnostic specificities and sensitivities ranged from 99.7% to 100% and from 98.8% to 100%, respectively. In this study, the Cobas Core Anti-HCV EIA proved to be a very convenient test, able to perform at the highest levels of sensitivity and specificity.