BACKGROUND An estimated 1% to 1.9% of North Americans are infected with the hepatitis C virus (HCV). Although Indigenous peoples are considered to bear the highest burden, there are only limited data regarding the demographic features and epidemiology of hepatitis C in this population.OBJECTIVES: To document the demographic characteristics, rates of newly diagnosed hepatitis C cases and prevalence of HCV infection in a Canadian First Nations population, and to compare the findings with an infected non-First Nations population.METHODS: A research database spanning 1991 to 2002 was developed, linking records from multiple clinical and administrative sources. Over a 12-year period, 671 First Nations and 4347 non-First Nations HCV-positive Canadians were identified in the province of Manitoba. Demographics, residence and time trends were compared between infected First Nations and non-First Nations persons.RESULTS: HCV-infected First Nations individuals were younger (mean [± SD] age 33.0±0.4 years versus 39.7±0.2 years; P<0.0001), more often female (60% versus 40%; P<0.0001) and more often resided in urban centres (73% versus 27%; P<0.001). The rate of newly diagnosed HCV cases was 2.5-fold (91.1 per 100,000 versus 36.6 per 100,000; P<0.000) and prevalence 2.4-fold (801.7 per 100,000 versus 334.8 per 100,000; P<0.000) higher among the First Nations relative to non-First Nations populations.CONCLUSIONS: The results of the present large population-based study indicate that the First Nations population with hepatitis C is characteristically different from infected non-First Nations persons. The results also describe higher rates of newly diagnosed cases and prevalence of HCV infection in the First Nations population. These findings should serve as an important baseline for future primary prevention and therapeutic intervention strategies in this high-risk population.