BACKGROUND: The potential for cellular cardiomyoplasty to provide functional left ventricular recovery in the chronically injured heart remains unclear. METHODS: Yorkshire swine (n = 10; 35-50 kg) had anterolateral myocardial infarction (MI) induced by coil embolization of the left anterior descending artery. Approximately 5 weeks post-MI, a composite, intravascular ultrasound-guided catheter system (TransAccess) was used to deliver an autologous, labeled, bone marrow-derived cell sub-population (approximately 3 x 10(8) cells) or saline control (approximately 50 injections/arm) through coronary veins directly into infarct and peri-infarct myocardium. Two months post-transplant, the animals had blinded endocardial and epicardial left ventricular electrical scar mapping and biventricular electrical stimulation. Coronary angiography and quantitative biplane ventriculography were performed at baseline, transplant, and sacrifice time-points. RESULTS: Robust, viable, predominantly desmin-negative cell grafts were demonstrated post-mortem in all treatment animals. Baseline and pre-transplant global and regional wall motion was similar between groups. The cell treatment group demonstrated functional recovery with a left ventricular ejection fraction of 38.1% at the time of transplant increasing to 48.5% (p = 0.005) at sacrifice, whereas the control arm was unchanged (38.0% vs 34.3%, respectively; p = NS). The regional improvement corresponded with a reduction in percentage of hypokinetic (52.1%-42.9%, p = 0.002) and percentage of akinetic (24.8%-17.7%, p = 0.04) segments in the cell-treated animals. Epicardial scar area was not different (37 cm2 vs 23 cm2, p = 0.37) between groups. CONCLUSIONS: Percutaneous, transvascular, direct intramyocardial bone marrow cell transplantation is safe and feasible in chronically infarcted tissue. In this pilot study, cell therapy improved overall left ventricular systolic function by recruiting previously hypokinetic or akinetic myocardial tissue.