The measurement of antibodies against hepatitis C virus (HCV) is important to screen HCV infection. The aim of this study is to investigate the reliability of 2 commercially available anti-HCV antibody kits used in routine laboratory testing in Egypt. One thousand nine hundred and thirty-one serum samples were analyzed using 2 anti-HCV test systems: Cobas e 411® Elecsys Anti-HCVII and Vidas® Anti-HCV Biomerieux. Discrepant samples were tested using the recombinant immunoblot assay Innogenetics® INNO-LIA HCV Score. Overall agreement of the 2 tests was 94%. Following discrepant sample testing by LIA, sensitivity and specificity using Vidas were 94% and 99%, respectively, while those for Cobas were 97% and 96%, respectively. This study demonstrates superior specificity by Vidas and higher sensitivity by Cobas. Both methods are suitable for laboratory and/or blood screening programs. The concomitant use of a supplementary or confirmatory assay is necessary to compare the accuracy of HCV serological assays.