Objectives: This study assessed the burden and determinants of cardiovascular and metabolic risk in a community sample of high risk Indigenous Australians. Background: Indigenous Australians are over-represented in the most disadvantaged strata of Australian society. The role of psychosocial and socioeconomic factors in patterning cardiometabolic disease in this population is unclear. Methods: The Heart of the Heart Study was a cross sectional study of 436 Aboriginal adults from remote, urban and peri-urban communities around Alice Springs (Northern Territory, Australia). Participants underwent detailed assessments of socio-demographic, psychosocial, cardiovascular and metabolic status. Results: Individuals with depression were twice as likely to have cardiovascular disease (OR 2.03; 1.07-3.88; p <0.05). Chronic kidney disease (39.7 , 37.2 and 18.2 ) and diabetes (28.4 , 34.0 and 19.2 ) were more common in peri-urban and remote compared to urban communities. Cardiovascular disease did not vary across locations (p = 0.069), but coronary artery disease did (p = 0.035 for trend). Unemployed individuals were more likely to have cardiovascular disease (OR 2.32; 1.33-4.06; p <0.001). Socioeconomic gradients in coronary artery disease, all cardiovascular disease and diabetes, as measured by income, operated differentially across locations (p for location/socioeconomic status interactions 0.002; 0.01 and 0.04 respectively). Conclusion: Participants had high rates of pre-existing cardiovascular disease, diabetes and chronic kidney disease. Cardiovascular risk in these communities was associated with psychosocial factors and socioeconomic indicators. However, gradients operated differentially across location. These data provide a strong foundation for better understanding key drivers of increased levels of cardiovascular and other common forms of non-communicable disease in Indigenous people.