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Objective Indigenous Australians have rates of cardiovascular (CVD) mortality some seven to 10-fold higher than non-Indigenous Australians aged 25-64 years. We aimed to evaluate the impact of type 2 diabetes and components of the metabolic syndrome on carotid intima-media thickness (CIMT) as a marker of cardiovascular risk in Indigenous Australians living in remote and urban environments and in Australians of European ancestry. Design, patients and measurements CIMT was measured by high-resolution B-mode ultrasound imaging of the common carotid artery in 119 remote Indigenous, 144 urban Indigenous and 122 urban European Australians with and without diabetes. Results In nondiabetic participants, CIMT was lowest in Europeans (mean (SD) 0.64 mm (0.10)), higher in urban Indigenous Australians (0.67 mm (0.12)) and highest in remote Indigenous Australians (0.73 mm (0.15), P < 0.001). CIMT was higher with diabetes with the same pattern observed between populations: 0.73 mm, 0.79 mm and 0.82 mm, respectively (P < 0.001). Traditional risk factors (age, male gender, blood pressure and HbA1c) explained 35-45% of the variance of CIMT within each population group. However, differences in CIMT between population groups were maintained after adjustment for these cardiovascular risks plus cholesterol and smoking (P < 0.001). Factor analysis revealed that variables of the metabolic syndrome, together with smoking and elevated C-reactive protein (CRP) and urinary albumin-creatinine ratio (ACR), are likely to explain the higher CIMT in Indigenous Australians (and the urban-remote gradient). Unmeasured variables (genetic, psychosocial and socioeconomic) may also contribute to higher CIMT in these populations. Conclusion Glycaemic control and metabolic syndrome components contribute significantly to premature atherogenesis in Indigenous Australians and we recommend that therapy should be targeted accordingly.