Stem cell treatment may positively influence recovery and inflammation after injury by multiple mechanisms, including the paracrine release of protective growth factors. Embryonic stem cells (ESC) are understudied and may have greater protective power than adult bone marrow stem cells (BMSC). We hypothesized that embryonic stem cell paracrine protective mechanisms in the heart (decreased injury by enhanced growth factor mediated reduction of proinflammatory cytokines) would be superior to the paracrine protective mechanisms of the adult stem cell population in a model of surgically induced global ischemia. Adult Sprague-Dawley rat hearts were isolated and perfused via Langendorff model. Hearts were subjected to 25 min warm global ischemia, 40 min reperfusion and randomly assigned into one of four groups: (1)vehicle treated; (2)BMSC or ESC pre-ischemic treatment; (3)BMSC or ESC post-ischemic treatment; (4)BMSC or ESC conditioned media treatment. Myocardial function was recorded, and hearts analyzed for expression of tissue cytokines and growth factors(ELISA). Additionally, ESCs and BMSCs in culture were assessed for growth factor production(ELISA). ESC treated hearts demonstrated significantly greater post-ischemic recovery of function(left ventricular developed pressure, end diastolic pressure, +/-dP/dT) than BMSC treated hearts or controls at end reperfusion. ESC conditioned media (without cells) also conferred cardioprotection at end reperfusion. ESC infused hearts demonstrated increased VEGF and IL-10 production compared to BMSC hearts. ESC hearts also exhibited decreased proinflammatory cytokine expression compared to MSC hearts. Moreover, ESCs in cell culture demonstrated greater pluripotency than MSCs. Embryonic stem cell paracrine protective mechanisms in surgical ischemia are superior to those of adult stem cells.