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Six major genotypes of the hepatitis C virus (HCV) have been described; it is assumed to be uncommon for genotypes to change in chronically infected individuals. Venous blood samples obtained from Vietnamese-Australian injecting drug users who participated in successive studies conducted in Melbourne, Australia, were genotyped using the Bayer line probe assay and genotype confirmed by sequencing whenever possible. Three changes of HCV genotype were observed, and one infection in an individual not exposed previously. The rate of change of genotype was 3 in 11.4 person-years (py), or 26.4 per 100 py (95% CI: 8.5, 81.6). Traditionally-calculated HCV incidence was 1 in 4.3 py, or 23.3 per 100 py (95% CI: 3.3, 165.1). These data imply that HCV genotype change in injecting drug users occurs at least as frequently as infections in naive individuals, and that traditionally-calculated HCV incidence rates represent a minority of actual HCV transmission among practicing injecting drug users.