Background: After acute myocardial infarction (AMI), the recovery of perfusion in infarct area may lead to significant spontaneous infarct size (IS) reduction during the subsequent period. The natural course of infarct-healing process after reperfusion therapy has not been fully elucidated. In this study, we investigated the time course of the spontaneous infarct-healing process in patients with reperfused AMI. Methods and Results: Fifty-two patients with AMI who underwent primary percutaneous intervention were included. IS was measured with single-photon emission tomography using Bull's eye method at 4th day, at 5th, and at 10th months. IS was expressed as a percentage of the total myocardium. IS decreased by 33.6% at 5th month when compared with 4th day IS (from 26.3% +/- 18.8% to 17.5% +/- 12.9%, P < 0.001, n = 44). At 10th month, mean IS decreased by 21% when compared with 5th month IS (from 15.89% +/- 12.65% to 12.53% +/- 9.35%, P = 0.007, n = 31) and 49% when compared with 4th day IS (24.02% +/- 17.67% to 12.53% +/- 9.35%, P < 0.001). Conclusion: Significant endogenous recovery of perfusion in the infarct area occurs at the long term in patients with reperfused AMI, Infarct healing is a dynamic and ongoing process and decrease in IS continues long term after reperfused AMI.