Background: In France, the first prevalence survey of hepatitis C virus (HCV) infection was conducted in 1994. Regarding the hepatitis B virus (HBV), prevalence studies of markers for this infection were conducted in the early 1990s, but in different populations. To obtain national estimates of HBV infection prevalence and update estimates for HCV infection, a new survey was conducted in 2004 among the population of metropolitan France. Methods: A two-stage sampling design was chosen. The first stage involved regional stratification of the territory and allowed for the selection of Health Examination Centers (CES) using a stratified random sampling technique. The second stage allowed for the selection of social security beneficiaries aged 18 to 80 years, stratified by age and socioeconomic status. Insured individuals were seen at the HSCs and, after providing consent, completed a questionnaire covering demographic, occupational, and behavioral data, as well as a history of possible exposure to HCV or HBV. Serum samples were tested for anti-HCV antibodies, HCV RNA, anti-HBc antibodies, and HBs antigen. The data were analyzed using SUDAAN® software. The results obtained (taking into account the sampling design and weighting) are estimates for the population of metropolitan France aged 18 to 80 years. Results: The overall prevalence of anti-HCV antibodies was 0.84% (95% CI: 0.65–1.10), corresponding to 367,055 people (95% CI: 269,361–464,750) found to be seropositive. Among those with positive anti-HCV antibodies, 57% (95% CI: 43–71) were aware of their seropositivity. Among those with positive anti-HCV antibodies, 65% (95% CI: 50–78) tested positive for HCV RNA, indicating that 221,386 people (95% CI: 158,909–283,862) had chronic hepatitis C. In multivariate analysis, the factors found to be significantly associated with the presence of anti-HCV antibodies were as follows: intravenous or nasal drug use, a blood transfusion received before 1992, tattooing, age over 29 years, living in precarious conditions, and being born in a country where the prevalence of anti-HCV antibodies is greater than 2.5%. The prevalence of HBs antigen was 0.65% (95% CI: 0.45–0.93), corresponding to 280,821 individuals (95% CI: 179,730–381,913) who were chronic carriers of HBs antigen. Among these individuals, 45% (95% CI: 23–69) were aware of their HBs antigen-positive status. The prevalence of anti-HBc antibodies was 7.3% (95% CI: 6.5–8.2), indicating that 3.1 million people (95% CI: 2.8–3.5) had had prior exposure to HBV. Factors found to be significantly associated with anti-HBc antibody positivity were: intravenous drug use, homosexuality, precarious living conditions, an educational level below the high school diploma, a stay of at least three months in institutions, a country of birth where the prevalence of HBs antigen is greater than 2%, a place of residence located in the Northeast, Southeast, or the Île-de-France region, being male, and being over 29 years of age. Conclusions: In 2004, the prevalence of anti-HCV antibodies was similar to the 1994 estimates, which were 1.05% (95% CI: 0.75–1.34). However, the prevalence of HBs antigen carriage is higher than previous results, which, depending on the study, ranged from 0.2% to 0.4%. This new prevalence survey highlights the need to strengthen screening for these two infections and target it toward the populations most at risk. (R.A.)