To use cardiac magnetic resonance (MR) imaging indices, injury biomarkers, and microscopy for quantifying the effects of defined microemboli volume and sizes on viability, left ventricular (LV) function, and perfusion in preexisting acute myocardial infarcts in a swine model. Institutional approval was obtained to perform x-ray fluoroscopy and 90-minute left anterior descending coronary artery occlusion-reperfusion (single ischemic insult) in 16 pigs and coronary embolization in eight of the 16 pigs (32 mm(3), 40-120 μm microemboli) (double ischemic insults). Another eight pigs served as controls. Cardiac MR imaging results (viability, function, and perfusion), injury biomarkers (creatine-kinase-MB and troponin I), and histopathologic evaluations were quantified. Analysis of variance was performed, and a P value less than .02 was considered to indicate a significant difference. Delayed contrast material-enhanced MR imaging allowed simultaneous visualization of hyperenhanced large infarcts, hypoenhanced microvascular obstruction (MVO) zones, and moderately enhanced patchy microinfarcts in border zones, which represent different degrees of contraction and perfusion in the respective regions, in pigs subjected to double ischemic insults. The increase in myocardial damage was smaller in pigs with double insults (15.7% ± 1.1% of total LV mass) than in those with a single insult (12.4% ± 1.2%, P < .02), but the reduction in LV ejection fraction was disproportional (32% ± 0.6% and 38% ± 1%, P < .02, respectively). Delayed contrast-enhanced imaging can allow quantification of the MVO zone but can result in underestimation of the extent of myocardial damage compared with microscopy in animals subjected to double insults (18.2 ± 1.6, P < .02). A significant increase in cardiac injury biomarkers was observed at 18-24 hours in both cohorts. The additional effect of microemboli on troponin I was demonstrated at 68-72 hours (3.2 ng/mL ± 0.85 [3.20 μg/L ± 0.85] vs 1.34 ng/mL ± 0.43 [1.34 μg/L ± 0.43], P < .02). MR imaging has the potential to allow visualization of acute myocardial infarcts, MVO zones, and patchy microinfarcts simultaneously. The accentuated LV dysfunction caused by double ischemic insults was linked to expansion of the MVO zone, perfusion deficits, and myocardial damage.