Preclinical and clinical studies have demonstrated that stem cell transplantation can improve the LV contractile performance yet the underlying mechanisms remain unknown. We examined whether mesenchymal stem cell transplantation (MSC)-induced beneficial effects are secondary to paracrine associated improvements in LV contractile performance, wall stress, and myocardial bioenergetics in hearts with postinfarction LV remodeling. Myocardial contractile function (MRI) and bioenergetics (31P NMR spectroscopy) were compared 4 weeks after AMI between normal pigs (Normal: n=6), untreated pigs with myocardial infarction (MI: n=6), and pigs receiving autologous MSC transplantation (MI+MSC: n=5). A distal LAD occlusion instigated significant myocardial hypertrophy. Ejection fraction (EF) decreased from 55.3±3.1% (normal) to 30.4±2.3% (MI) (p<0.01) and 45.4 ± 3.1% (MI+MSC: p<0.01 vs. MI). Hearts in the MI group developed significant contractile dyskinesis in the infarct zone (IZ) and border zone (BZ). MSC transplantation significantly improved contractile performance from dyskinesis to active contraction (p<0.01 vs. MI). BZ systolic wall stress was severely increased in MI hearts, but significantly improved following MSC transplantation (p<0.01 vs. MI). The BZ demonstrated profound bioenergetic abnormalities MI pigs; this was significantly improved following MSC transplantation (p<0.01 vs. MI). Patchy spared myocytes were found in the IZ of hearts receiving MSC transplantation but not in control hearts. These data demonstrate MSC transplantation into the BZ causes significant improvements in myocardial contractile performance and reduction in wall stress resulting in significant bioenergetic improvements. Low engraftment indicates that MSCs did not provide a structural contribution to the damaged heart; observed beneficial effects likely resulted from paracrine repair mechanisms.