Background: Different blood groups respond in a different way to environmental stimuli, thereby different blood groups must have different vulnerability to human illnesses. Objective: To find out an association of ABO blood group distribution and ischemic heart disease (IHD). Materials and Methods: A prospective study, in a sample of 410 patients attending the medicine OPD, was done in a tertiary-care hospital to find out an association of ABO blood group distribution and IHD. Result: Of 410 patients, 226 patients were of myocardial infarction (MI) and 133 of angina. MI was seen predominantly in blood group “B” subjects (38.49%) and angina in blood group “A” subjects (37.59%). The highest numbers of men with MI were in the age group 31–40 and 41–50 years. Occurrence of MI among women was common in 20–30 and 31–40 years age group, and the highest number of them belonged to blood group “A”. While 57.14% male patients with angina belonged to blood group “O” and were in the age group of 41–50 years. Majority of women with blood group “A” presented with angina in 31–40 years age group, blood group “B” in 20–30 years age group, “AB” blood group in 41–50 years age group, and blood group “B” in 31–40 years age group. Conclusion: IHD was more common among men when compared with women. The ratio of male to female with MI was 1.4:1 and, for angina, 1.1:1. The occurrence of IHD was highest among subjects with age younger than 40 years. The incidence of IHD was three times more among blood groups A and B subjects when compared with blood group O subjects, whereas the highest incidence of MI was seen among subjects with blood group B. Men with blood group B and women with blood group A showed higher prevalence of MI, whereas angina was more common among A blood group patients of both sexes.