Background: Coronary artery disease (CAD) remains the leading cause of death amongst Indigenous Australians accounting for 12.1% of all deaths in this population. However, there is little evidence to suggest that Indigenous status is an independent risk factor for the development of coronary artery disease. This study assessed the association between Indigenous status and the severity of CAD in patients presenting with chest pain at a regional hospital emergency department. Methods: This was a retrospective single-centre audit over 12 months from January to December 2017. Charts were reviewed for both Indigenous and non-Indigenous patients 18 years and older who presented with chest pain and subsequently underwent an invasive coronary angiogram. Multivariable logistic regression was performed to examine the association of Indigenous status with the severity of CAD. Results: Indigenous patients are 2.7 times more likely to experience significant CAD compared to non-Indigenous patients (Adjusted odds ratio [AOR]=2.73, 95% CI [1.38, 5.39], p≤0.001) even after adjusting for other risk factors. Those aged 65 years and older are more prone to significant CAD (AOR=2.96, 95% CI [1.12, 7.78], p=0.03), while women were less likely to have significant CAD compared to men, (AOR=0.46, 95% CI [0.27, 0.78], p<0.01). Conclusion: In this study cohort, our analysis indicates that there is a strong association between Indigenous status and significant coronary artery disease, independent of the increased burden of traditional cardiovascular risk factors among Indigenous Australians.