This study sought to determine the prevalence of spontaneous reperfusion of an infarct-related artery (IRA) and associated myocardial salvage in the absence of thrombolysis or angioplasty. Twenty-one patients with acute myocardial infarction received only heparin and aspirin. At a median of 18 hours after presentation, 12 patients (57%) had angiographic patency of the IRA. Technetium-99m sestamibi was injected acutely on presentation and again at hospital discharge. Acute and final perfusion defect sizes were measured. Their difference, myocardial salvage, was calculated along with salvage index (myocardial salvage/acute defect). Comparing patients with a patent versus occluded IRA, myocardium at risk was similar (16% +/- 12% vs 12% +/- 9% left ventricle, p = NS); however, myocardial salvage (9% +/- 9% vs -2% +/- 7% left ventricle, p = 0.01), and salvage index (0.62 +/- 0.37 vs 0.19 +/- 0.33, p = 0.01) were greater in patients with spontaneous reperfusion. Resolution of chest pain was greater in patients with a patent IRA (100% vs 55%, p = 0.003). Spontaneous reperfusion of the IRA occurs frequently in patients with acute myocardial infarction and is associated with significant myocardial salvage.