Before the routine screening of donor blood for hepatitis C virus (HCV) began in 1992, patients who received blood transfusions were at increased risk for HCV infection. Patients with congenital heart disease requiring surgery were at particular risk because of the large volume of blood products required. It was hypothesized that patients who had congenital heart surgery before 1992 would have a high prevalence of HCV infection and would benefit from routine screening as part of cardiologic follow-up. HCV screening is performed on all patients in the Adult Congenital Cardiac Program at the investigators' center. Of 198 patients who underwent heart surgery before 1992, 17 (8.6%) had positive HCV antibody results, and 8 (4.0%) had positive HCV ribonucleic acid results. Only 1 of these patients had elevated serum transaminase levels at the time of screening. In conclusion, the data from this study demonstrated an approximately fivefold increased prevalence of HCV infection in adults with congenital heart disease compared with the aged-matched general population. Serum transaminase levels are not a valid screening method. The long-term significance of HCV in this population is not known. Routine HCV screening for all patients who underwent cardiac surgery before 1992 is recommended.