Summary. Egypt is the country with the largest hepatitis C virus (HCV) epidemic in the world. In 2008, a Demographic Health Survey (DHS) was carried out in Egypt, providing for the first time a unique opportunity for HCV antibody testing on a nationwide representative sample of individuals. Consenting individuals answered a questionnaire on socio-demographic characteristics and iatrogenic exposures, before providing a blood sample for HCV antibody testing by enzyme-linked immunosorbent assay. Factors independently associated with HCV infection were examined through multivariate logistic regression models. Of 12 780 eligible subjects aged 15–59 years, 11 126 (87.1%) agreed to participate and provided a blood sample. HCV antibody prevalence nationwide was 14.7% (95% CI 13.9–15.5%) in this age group. HCV antibody prevalence gradually increased with age, reaching, in the 50–59 years age group, 46.3% and 30.8% in males and females, respectively. It was higher in males compared to females (17.4% versus 12.2%, respectively, P < 0.001), and in rural compared to urban areas (18.3% versus 10.3%, respectively, P < 0.001). In multivariate analysis, age, male sex, poverty, past history of intravenous anti-schistosomiasis treatment, blood transfusion, and living outside of the Frontier Governorates were all significantly associated with an increased risk of HCV infection. In addition, in urban areas, lack of education and being circumcised for females were associated with an increased risk of HCV infection. This study confirmed on a nationwide representative sample the very high HCV antibody prevalence in Egypt. It stresses the urgent need for strengthening prevention efforts, and bringing down the costs of antiviral drugs for countries like Egypt, where the people in the most precarious situations are also those most likely to be infected by the virus.