BACKGROUND Several studies suggested that exercise training might improve myocardial perfusion by inducing coronary vascular adaptations or enhancing collateralization. However, these findings were obtained in patients with chronic coronary artery disease using thallium-201 myocardial perfusion scintigraphy. We evaluated whether a long-term exercise-based cardiac rehabilitation (CR) started early (9 ± 3 days) after ST elevation acute myocardial infarction (STEMI) improves myocardial perfusion and left ventricular (LV) function, evaluated by gated single-photon emission computed tomography (SPECT) imaging. METHODS Randomized controlled study. METHODS Fifty patients with recent STEMI were randomized into two groups: 24 enrolled in a 6-month exercise-based CR programme (group T) and 26 discharged with generic instructions for maintaining physical activity and correct lifestyle (group C). All patients underwent cardiopulmonary exercise test and gated SPECT within 3 weeks after STEMI and at 6-month follow up. RESULTS At follow up, group T showed a significant reduction of stress-induced ischaemia (p < 0.01) and an improvement in resting and post-stress wall motion (both p < 0.005) and resting (p < 0.05) and post-stress wall thickness (p < 0.005) score indexes. At follow up, group T showed an improvement in peak oxygen consumption (p < 0.0001), O(2) pulse (p < 0.05), and in the slope of increase in ventilation over carbon dioxide output (p < 0.001). No changes in myocardial perfusion parameters, LV function, and cardiopulmonary indexes were observed in group C at follow up. CONCLUSIONS Six months of exercise training early after STEMI reduces stress-induced ischaemia and improves LV wall motion and thickness. Exercise-induced changes in myocardial perfusion and function were associated with the absence of unfavourable LV remodelling and with the improvement of cardiovascular functional capacity.