AIM: There is limited information on the natural history of HCV infection in China. We investigated the outcome of HCV infection after nine-year follow-up and the risk factors in blood donors in China in order to provide the foundation for prevention and therapy. METHODS: A total of 172 cases of HCV infection with anti-HCV positive and ALT abnormality were enrolled in the archives when was screened blood in Hebei Province in 1993. In them 142 blood donors were followed up till July 2002. No antiviral treatment was applied to them during the period of infection. In the present study, anti-HCV, HCV-RNA and aminotransferase were detected and genotyping was conducted by the method of restriction fragment length polymorphism (RFLP). B-type ultrasound detection was performed in all the patients. Age, sex, alcohol consumption and clinical symptoms were questioned. RESULTS: After nine years' follow-up, 10.56% (15/142) of the cases were negative for anti-HCV and 16.42% (12/134) of them were negative for HCV-RNA. The genotypes 1b, 2a and 1b/2a were 91.07%, 6.25% and 2.68% respectively. Twelve cases (8.45%) were negative for both HCV-RNA and anti-HCV. The rate of chronicity in this group was 83.58% (112/134), and the rate of viral spontaneous resolution was 16.42% (22/134). The mean level of ALT, AST, γ−GT in HCV RNA positive cases was significantly higher than that in HCV RNA negative cases (P<0.001). The abnormal rate of ALT and/or AST in male donors was significantly higher than that in female donors (P=0.005). The rate of progression to liver irrhosis from chronic hepatitis C was significantly higher in the cases of super-infection with HBV than that in the cases of single HCV infection. Overdose alcohol consumption promoted the progression to chronicity. CONCLUSION: This area (Hebei Province) has a higher rate of chronicity in HCV infection, and measures should be taken to prevent its progression to serious liver diseases, especially for patients super-infected with HCV and HBV.