Aggressive clinical and public health interventions have resulted in significant reduction in coronary artery disease (CAD) worldwide. However, South Asian immigrants (SAIs) exhibit the higher prevalence of CAD and its risk factors as compared with other ethnic populations. The objective of the current study is to assess the prevalence of metabolic syndrome (MS), its association with high density Lipoprotein (HDL) function, Apo lipoprotein A-I (APOA1) gene polymorphisms, and sub-clinical CAD using common carotid intima-media thickness (CCA-IMT) as a surrogate marker. A community-based cross-sectional study was conducted on SAIs aged 35-65 years. Dysfunctional/pro-inflammatory (Dys-HDL) was determined using novel cell free assay and HDL inflammatory index. Six intronic APOA1 gene polymorphisms were analyzed by DNA sequencing. According to the International Diabetes Federation definition, MS prevalence was 29.7% in SAIs without CAD and 26% had HDL inflammatory index ≥ 1 suggesting pro-inflammatory Dys-HDL. Six novel APOA1 single nucleotide polymorphisms (SNPs) were analyzed with logistic regression, three SNPs (G2, G3, and G5) were found to be significantly associated with MS (p = 0.039, p = 0.038, p = 0.054). On multi-variate analysis, MS was significantly associated with BMI > 23 (P = 0.005), Apo-A-I levels (p = 0.01), and Lp [a] (p < 0.0001). SAIs are known to be at a disproportionately high risk for CAD that may be attributed to a high burden for MS. There is need to explore and understand non-traditional risk factors with special focus on Dys-HDL, knowing that SAIs have low HDL levels. Large prospective studies are needed to further strengthen current study results.