ABSTRACT: To understand the prevalence of hepatitis C virus (HCV) infection in blood donors over a nearly 27-year interval and to explore the factors that affect the outcome of HCV infection.A retrospective and cross-sectional study was conducted. The participants, mostly plasma donors, were selected from three administrative villages in the Jiangsu province in Eastern China. A questionnaire was administered among the villagers who had a history of blood donation from the late 1980s to the early 1990s. All participants underwent physical examination, liver B-ultrasonography, and liver stiffness measurement. In addition, 10 mL of blood was collected from each participant to measure simple liver function parameters (albumin, alanine aminotransferase, aspirate aminotransferase), blood factors (platelet), and for hepatitis B surface antigen, antiHCV, and antihuman immunodeficiency virus detection. HCV RNA detection, HCV genotyping, and other tests were carried out in antiHCV-positive patients.After a median of 27 years (25-31 years) from the last blood donation to the time of survey, a total of 1694 participants were investigated, and the antiHCV-positive individuals were categorized into three groups: blood donors (n = 12, 3.3%), plasma donors (n = 534, 68.5%), and mixed donors (n = 324, 58.8%). A total of 592 (68.05%) patients had detectable HCV RNA, and 91.9% had genotype 1b. A total of 161 (27.2%, 161/592) patients with chronic HCV were considered to have cirrhosis with a liver stiffness measurement level higher than 12 kPa. Multiple logistic (binary) regression analysis results showed that platelet and IgG levels were associated with cirrhosis.The nearly 27-year interval investigation revealed that chronic hepatitis C infection is a very serious public health problem in Eastern China. Plasma donation and subsequent return of blood cells to the donor are the main causes of hepatitis C infection. The main HCV genotype is 1b. Nearly 28% of cases progressed to cirrhosis. Age, especially over 60 years, and regular drinking habits were risk factors associated with cirrhosis.