To analyze the impact of ABO groups on coronary heart disease risk factors, coronary involvement and prognosis.An observational single center study was conducted to examine 4901 consecutive patients with heart disease receiving coronary angiography and ABO group determination at National Research Council Institute of Clinical Physiology between January 1993 and December 2003, with maximum 10 years follow-up. All-cause death and cardiac death, were the considered end points.When compared to the official distribution of ABO groups in the Italian population (O 40%, A 36%, B 17%, AB 7%), a substantially different distribution was observed in the study population (O 43.3%, A 41.4%, B 11.2%, AB 4.1%). In addition, a significant association was found between group non-O and family history of ischemic heart disease, hypercholesterolemia and presence of coronary atherosclerosis. Higher prevalence of A and B alleles was found in patients with myocardial infarction (P<0.05). Group non-O was a powerful predictor of cardiac mortality in patients aged <65 years, particularly in women (HR 1.53, 95% CI 1.06-2.21 and HR 5.29, 95% CI 1.57-17.82, respectively).Group non-O is associated with increased mortality in patients with ischemic heart disease. Group non-O increases the risk for cardiac death in non-elderly patients, particularly in younger females, and groups A and B prevail in myocardial infarction. ABO group determination might aid in genetic screening for ischemic heart disease and become relevant in the management of risk factor control.