Treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) is monitored by assessing plasma HCV-RNA load. However, detection of HCV core antigen (HCVcAg) may be an alternative. To evaluate the diagnostic performance of the HCVcAg assay to monitor the efficacy of DAAs in HCV-infected patients METHODS: We performed searches in multiple electronic databases until 6 July 2022, of studies evaluating the HCVcAg detection in plasma or serum compared with the HCV-RNA test (gold standard). We calculated pooled measurement at 2 and 4 weeks of treatment, and at end-of-treatment (EOT), as well as sustained virological response (SVR; 12 weeks after EOT). We selected 16 studies from 2016 to 2022, with 3237 patients and 8958 samples. Overall, the diagnostic performance and clinical utility of the HCVcAg assay were poor at week 2 (sensitivity=0.40, specificity=0.96, positive likelihood ratio (PLR)=9.16, negative likelihood ratio (NLR)=0.63, and area under the summary receiver operating curve (SROC)=0.57), fair at week 4 (sensitivity=0.30, specificity=0.90, PLR=3.18, NLR=0.77, and AUC=0.79), acceptable at EOT (sensitivity=0.40, specificity =0.98, PLR=16.54, NLR=0.62, and AUC=0.97) and excellent for SVR (sensitivity=0.94, specificity=0.99, PLR=107.54, NLR=0.06, and AUC=0.99). The HCVcAg assay may be helpful for monitoring the efficacy of HCV treatment with DAAs in HCV-infected patients at EOT and for documenting SVR, but not at weeks 2 and 4 of treatment due to poor diagnostic performance.