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Bone marrow (BM) stem cells improve cardiac function and outcome after acute ST-segment elevation myocardial infarction (MI). In this randomized controlled trial, the effects of intracoronary transfer of autologous BM cells on left ventricular ejection fraction (LVEF) and volumes (2D-echo and resting SPECT), stroke volume [impedance cardiography (ICG)], autonomic control [heart rate variability (HRV)], baroreflex sensitivity (BRS), and exercise tolerance (cardiopulmonary exercise test) were assessed in post-MI patients. Exercise stress SPECT was also performed.After percutaneous coronary intervention (PCI), 38 patients with residual LV dysfunction were randomized to either the BM group (optimized treatment plus intracoronary transfer of autologous BM cells 4 ± 1 days after PCI, n = 19) or control (C) group (optimized treatment only, n = 19). After 12 months, mean LVEF (%) increased 13.1 ± 1.9 in the BM patients vs. 5.3 ± 2.0 in C, with an increase in stroke volume (mL, 14.5 ± 4.0 in BM vs. 1.8 ± 3.7 in C) associated with improved HRV [SD (ms) 62.4 ± 8.3 in BM vs. 19.0 ± 7.5 in C), higher BRS (ms/mmHg, 8.0 ± 1.8 in BM vs. –1.9 ± 1.7 in C), and peak VO2 (mL/kg min−1, 3.5 ± 1.0 in BM vs. −0.4 ± 0.5 in C). Stress SPECT showed improvements in perfusion, regional and global LV function scores (P < 0.05 BM vs. C groups for all comparisons). Cell transfer did not increase the risk of adverse clinical, in-stent restenosis, or proarrhythmic events.The beneficial effect of autologous BM cells in post-MI patients with depressed LV function may be mediated by restoration of autonomic control, and improved exercise tolerance.