Coronary Artery Disease (CAD) is caused by plaque buildup in the wall of the arteries that carry blood to the heart. Aim: This is an analytical case-control study carried out at Al-Neelain University and samples from Sudan Heart center, Khartoum, Sudan, during November 2018 and aimed to detect the association of thrombomodulin G33A polymorphism and CAD. A total of 80 subjects have participated in the current research. 40 of them were known Sudanese Patients diagnosed with Coronary Artery Disease, admitted to Sudan heart center, 21(52.5%) were males and19 (47.5%) were females; their mean age is 56.6 years. Other 40 normal healthy volunteers similar in gender and age the case group used as a control group. 2.5 ml of EDTA anticoagulated blood was collected from all participants. DNA was extracted by the salting-out method. Then the detection of thrombomodulin G33A polymorphism using allele-specific Polymerase Chain Reaction. The data were obtained by using a directly structured interviewer questionnaire. Data were analyzed via (SPSS) software version 25. This study revealed that the thrombomodulin gene G33A polymorphism was statistically significantly associated with Sudanese patients with CAD (p value=0.00). This study concludes that the thrombomodulin G33A polymorphism predicts as a risk factor of the development of CAD in Sudanese patients.