BACKGROUND: Previous animal studies have demonstrated that the transmural extent of acute myocardial infarction defined by contrast-enhanced MRI (ceMRI) relates to early restoration of flow and future improvements in contractile function. We tested the hypothesis that ceMRI would have similar predictive value in humans. METHODS AND RESULTS: Twenty-four patients who presented with their first myocardial infarction and were successfully revascularized underwent cine and ceMRI of their heart within 7 days (scan 1) of the peak MB band of creatine kinase. Cine MRI was repeated 8 to 12 weeks later (scan 2). The transmural extent of infarction on scan 1 and wall thickening on both scans were determined using a 72-segment model. A total of 524 of 1571 segments (33%) were dysfunctional on scan 1. Improvement in segmental contractile function on scan 2 was inversely related to the transmural extent of infarction on scan 1 (P=0.001). Improvement in global contractile function, as assessed by ejection fraction and mean wall thickening score, was not predicted by peak creatine kinase-MB (P=0.66) or by total infarct size, as defined by MRI (P=0.70). The best predictor of global improvement was the extent of dysfunctional myocardium that was not infarcted or had infarction comprising <25% of left ventricular wall thickness (P<0.005 for ejection fraction, P<0.001 for mean wall thickening score). CONCLUSION: In patients with acute myocardial infarction, the transmural extent of infarction defined by ceMRI predicts improvement in contractile function.