Background and study aim: Hepatitis C virus (HCV) infection is a major public health problem worldwide. Blood donations screening achieved mainly by serological identification of HCV-Antibody (Ab), has largely reduced HCV transmission. HCV Core Antigen (CAg) tests have been introduced to supplement anti-HCV tests and HCV PCR analyses. CAg may be a useful screening test for identifying window phase of HCV infected patients whom are candidate for blood donations. The study aimed to evaluate diagnostic performance of HCV core antigen in comparison to HCV-RNA quantification and anti-HCV-Ab analyses in attendances of blood bank of Zagazig University hospitals. Patients and Methods: The study was performed on 92 participants attending the blood banks of Zagazig University Hospitals for blood donation between May 2015 to November 2017. The participants were classified into two groups; group A, which included 46 donors (32 males and 14 females) with negative HCV antibody and group B, which Included 46 patients (30 males and 16 females) with positive HCV antibody. Clinical assessment, HCV AB detection by ELISA, Prototype ELISA for HCV core antigen for presence of HCV core antigen and HCV RNA Quantitative were done for all participants. Results: No significant differences between both studied regarding sex and age. A high significant relation between HCV AB positivity and negativity as regard HCV PCR was found in both groups. A high significant relation between HCV core antigen positivity and negativity as regard HCV PCR. There was high significant relation between HCV core antigen positivity and HCV PCR in group A patients. There was a high significant relation between HCV core antigen positivity and HCV PCR in positive HCV antibody patients and statistically a high significant relation between HCV core antigen negativity and HCV PCR in group B patients. Conclusion: HCV core Ag can be identified by serological ELISA. This assay is cheap, easily performed, and compatible with HCV PCR. Its application may prevent the vast majority of HCV transmissions caused by the transfusion of window phase donations.