Cardiovascular disease in the number one cause of death worldwide, and it has been the most common cause of death in the United States each year since 1900. Today, one in every three adults is living with cardiovascular disease. Importantly, Veterans are more likely than non-Veterans to develop cardiovascular disease. In 2012, the National Center for Health Statistics reported that Veterans were more likely than non-Veterans to experience two or more chronic conditions such as heart disease, hypertension, and stroke (Kramarow and Pastor, 2012). Moreover, Veterans with post-traumatic stress disorder and Agent Orange exposure are at higher risk of developing heart disease. Specifically, the Department of Veterans Affairs formally recognized the association between Agent Orange exposure and ischemic heart disease in 2010, while the Millenium Cohort Study found that active duty Service members who were deployed and saw combat were at twice the risk of a newly developed cardiovascular disease than those Service members who were deployed without combat exposure (Crum-Cianflone et al., 2014). Finally, congenital heart defects are the most common form of birth defect in the general population, but in children of women with military service the incidence is increased. Congenital heart disease and other cardiovascular diseases can progress to heart failure. The only cure for end-stage heart failure is cardiac transplantation, but, due to the shortage of organs for transplantation, relatively few patients receive such lifesaving therapy. Patients that do receive a heart transplant require medications to prevent rejection of the heart, and these medications often have long-term side effects that also limit survival. The ultimate goal of our research proposal is to generate a human organ (a heart) in pigs, which will serve as an unlimited source of hearts for transplantation and provide a large animal model to study the regeneration of the human heart and/or the response of a human heart to experimental medications. We have teamed up with a world-leading research group to provide complementary expertise to achieve our goals and ensure that all potential ethical issues are well considered. Our preliminary data demonstrate that we have established state-of-the-art technologies using human-induced pluripotent stem cell populations to provide a platform for our proposed studies. Our preliminary data provide the rationale and establish the feasibility for our specific aims. We believe that the proposed studies will revolutionize cardiovascular care and ultimately lead to a cure for heart disease. Importantly, our proposed studies will benefit our military personnel, our Veterans, their families and have a tremendous impact on our society.