Large cohorts of persons infected with hepatitis C virus (HCV) that include patients with multiple risk exposures and behaviors have been rarely reported. We herein describe a population-based cohort of 759 Alaska Natives (AN) with HCV who were recruited into a long-term follow-up study. History of injection drug use (IDU) was reported by 60.1% and blood transfusion by 14.0%. The most common genotype was 1a (42.0%), followed by 1b (20.3%), 2b (14.7%), 3a (14.3%), and 2a (7.8%). By multivariable analysis, risk exposures (blood transfusion vs. other; P /=2 million copies/mL was associated with male gender (OR, 1.94) and genotype (P