BACKGROUND Hepatitis C virus (HCV) core antigen has been proposed as a surrogate marker of HCV replication. HCV core antigen detection and quantification can thus theoretically be used instead of nucleic acid testing (NAT) to diagnose infection and manage antiviral therapy, with several advantages compared to HCV RNA assays. HCV core antigen can now be easily detected and quantified by means of a chemiluminescent microparticle immunoassay on the Abbott Architect device. OBJECTIVE The aim of the present study was to evaluate the clinical performance of the Architect HCV Ag assay for the detection and quantification of HCV core antigen in patients with chronic HCV genotype 1-6 infections. RESULTS The Architect HCV Ag assay had a specificity of 100% (95%CI: 97.8-100%). HCV core antigen levels were not influenced by the HCV genotype. The lower limit of detection of 3fmol/L corresponded to approximately 1000IU/mL of HCV RNA, regardless of the real-time PCR assay used. HCV core antigen and HCV RNA levels correlated for HCV genotype 1-4 (r=0.89 and r=0.88 for the m2000 and the CAP/CTM v2.0 assay, respectively). CONCLUSIONS The Architect HCV Ag assay is highly specific and easy to perform. It represents a valuable screening, diagnostic and monitoring tool, especially in the era of new all-oral, interferon-free antiviral strategies that do not require high analytical sensitivity.