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Background: Hepatitis C virus [HCV] infection is a global health problem. Children with certain risk factors are at high risk of infection.Objective: The present study aimed to evaluate the prevalence of HCV among high-risk Egyptian children.Methods: The study included 1357 children aged 3-15 years with risk factors of HCV including receiving blood products, hemodialysis, previous surgical intervention, insulin therapy and positive family history. They were subjected to careful history taking, thorough clinical examination and routine laboratory investigations. All children were tested for HCV antibodies using commercial 4th generation enzyme-linked immunosorbent assay [ELISA] kits. Those with positive results were further assessed using polymerase chain reaction [PCR].Results: Among the studied patients, there were 89 children [6.6 %] with positive HCV Ab and 73 children [5.4 %] with positive PCR test for HCV. Using multivariate logistic regression, significant predictors of HCV infection in the studied children were blood transfusion [OR: 1.23, CI: 0.019-13.4], Intravenous [IV] injection [OR: 10.962, CI: 1.937-62.026] and previous operation [OR: 3.12, CI: 1.046-31.6].Conclusion: HCV infection is highly prevalent among high-risk children. Blood transfusion, IV injection and exposure to surgery are independent risk factors for infection in this population.