We have recently identified endothelial colony forming cells (ECFCs) in human blood and blood vessels, and ECFC are elevated in patients with coronary artery disease. Because pigs are a favored model for studying myocardial ischemia, we questioned whether ECFCs also exist in swine and whether myocardial ischemia would alter the number of ECFC in circulation. ECFCs were present in circulating blood and aortic endothelium of healthy pigs. In pigs with an acute myocardial infarction (AMI) (n = 9), the number of circulating ECFC was markedly increased compared to sham control pigs (15 ± 6 vs. 1 ± 1 colonies/100 cc blood, p < 0.05). Moreover, the percentage of circulating high proliferative potential ECFCs (HPP-ECFCs) was significantly increased following AMI induction compared to sham control (38.4 ± 5.8% vs. 0.4 ± 0.4%, p < 0. 05) and to baseline (38.4 ± 5.8% vs. 2.4 ± 2.4%, p < 0. 05) blood samples. This is the first study to report that ECFCs are present in blood and aorta in healthy pigs and that the number and distribution of circulating ECFCs is altered following AMI. Because circulating ECFC are also altered in human subjects with severe coronary artery disease, the pig model of AMI may be an excellent preclinical model to test the role of ECFC in the pathophysiology of AMI.