The purpose of this study was to compare hepatitis C virus (HCV) incidence and recent patterns of transmission within Aboriginal and non-Aboriginal Canadians. Cases of newly acquired HCV infection (in patients > or =15 years) reported to the Enhanced Hepatitis Strain Surveillance System from six jurisdictions in Canada were analyzed. Information on demographic and clinical characteristics as well as risk factors for HCV infection was collected using standardized questionnaires. Univariate analysis showed Aboriginal patients to be significantly more likely than non-Aboriginal patients to report injection drug use (77.1% vs. 64.0%; p < 0.05), to be female (54.6% vs. 37.6%; p < 0.05), to report high-risk sexual behaviors (48.6% vs. 34.1%, p < 0.05), and to report drug snorting (45.7% vs. 32.7%, p < 0.05). The median age of Aboriginal patients was significantly younger than that of non-Aboriginal patients (31 years [range, 15-71] vs. 34 years [range, 15-81]; p < 0.05). The overall incidence of HCV infection per 100,000 people aged 15 years and older was 18.9 (95% confidence interval [CI] 15.5-23.1) in Aboriginal people and 2.8 (95%CI 2.6-3.1) in non-Aboriginal people. Poisson regression analysis revealed that Aboriginal Canadians were more likely than non-Aboriginal Canadians to develop acute hepatitis C (adjusted rate ratio 5.8, 95%CI 4.7-7.3). An appropriate and effective public health strategy that includes planned and implemented prevention programs in partnership with the Aboriginal community is needed.