There are mounting evidences of relationship of different blood groups to disease. For many years, ABO blood group has been associated with predisposition to both arterial and venous disorders, such as venous thromboembolism, peripheral vascular disease and coronary artery disease. To evaluate the relationship of ABO and Rhesus blood groups with coronary artery disease. Total ninety five patients with coronary artery disease admitted in the Cardiac Surgery Department of Zarina Sikhder Women Medical College, Dhaka, and ninety five healthy stuff of same Medical College were studied. Their ABO and Rhesus Blood Groups were determined by standard method in the department of Transfusion Medicine, Zarina Sikhder Women Medical College, Dhaka, Bangladesh with full support from the department of Transfusion Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. The results obtained in this study show that the prevalence of Coronary Artery Disease (CAD) in blood group O is invariably higher than in all other ABO blood groups (p<0.05). It is striking that despite the fact that the most prevalent blood group among Bangladeshi people is phenotype B, the prevalence of CAD risk is associated with phenotype O (Odd ratio 2.034, 95% confidence interval 1.127 to 3.67). This suggests that a certain CAD risk is associated with phenotype O. Thus we conclude that, in Bangladeshi people, blood group phenotype O is associated with a substantially increased risk for CAD.