Background: The prevalence of coronary artery disease (CAD) considerably varies by ethnicity. High-risk populations include patients from Eastern Europe (EEP), the Middle East and North Africa (MENAP) and South Asia (SAP). Methods: This retrospective study aims to highlight cardiovascular risk factors and specific coronary findings in high-risk immigrant groups. We examined the medical records and coronary angiographies of 220 patients from the above-mentioned high-risk ethnic groups referred for Acute Coronary Syndrome (ACS) and compared them with 90 Italian patients (IP) from 2016 to 2021. In the context of high-risk immigrant populations, this retrospective study aims to shed light on cardiovascular risk factors and particular coronary findings. We analyzed the medical records of 220 patients from the high-risk ethnic groups described above referred for ACS and compared them with 90 IPs between 2016 and 2021. In addition, we assessed coronary angiographies with a focus on the culprit lesion, mainly evaluating multi-vessel and left main disease. Results: The mean age at the first event was 65.4 ± 10.2 years for IP, 49.8 ± 8.5 years for SAP (Relative Reduction (ReR) 30.7%), 51.9 ± 10.2 years for EEP (ReR 26%) and 56.7 ± 11.4 years for MENAP (ReR 15.3%);p< 0.0001. The IP group had a significantly higher prevalence of hypertension. EEP and MENAP had a lower prevalence of diabetes. EEP and MENAP had a higher prevalence of STEMI events; SAP showed a significant prevalence of left main artery disease (p= 0.026) and left anterior descending artery disease (p= 0.033) compared with other groups. In SAP, we detected a higher prevalence of three-vessel coronary artery disease in the age group 40–50. Conclusions: Our data suggest the existence of a potential coronary phenotype in several ethnicities, especially SAP, and understate the frequency of CV risk factors in other high-risk groups, supporting the role of a genetic influence in these communities.