Background. Coronary heart disease (CHD) is among the leading causes of death in Kuwait. This case-control study investigated the genetic association of APOB rs11279109 with CHD in Kuwaitis. Methods. The polymorphism was genotyped in 734 Kuwaiti samples by direct amplification. Statistical analysis with genetic modeling was used to assess its association with CHD. Results. A statistically significant association (P<0.001) between the rs11279109 DD genotype (OR: 2.43, CI: 1.34–4.41) with CHD was observed. A codominant genetic model revealed a 2.69 risk increase (CI: 1.57–4.61) for the DD genotype (P=0.009) independent of age, sex, BMI, smoking, hypercholesterolemia, and ethnicity suggesting APOB rs11279109 as an indicator for the increased risk of CHD. Conclusion. The DD genotype may explain molecular mechanisms that underline increased LDL oxidation leading to arthrosclerosis. The findings emphasize the need to identify genetic markers specific to the CHD patient ethnic group in order to improve prognosis and help in early diagnosis and prevention.