Background: Previous studies have shown beneficial effects of hepatocyte growth factor (HGF) gene on myocardial perfusion and infarction size, but not on regional strain in relation to global LV function. A non-invasive MR study was performed to determine the effect of a new HGF-gene (VM202), expressing two isoforms of HGF, on regional and global LV function. Methods and Results: Pigs (8/group) were divided into; 1) controls without infarction, 2) reperfused infarcted-controls and 3) infarcted-treated (1 hour after reperfusion) with VM202 injected at eight sites. Cine, tagging and delayed enhancement MR images were acquired at 3 and 50±3 days after infarction. At 50 days, EF in infarcted-treated animals increased (38±1% to 47±2%, p<0.01) to the level of controls without infarction (52±1%, p=0.16), but decreased in infarcted-controls (41±1% to 37±1%, p<0.05). Two-dimensional strain improved in remote, peri-infarcted and infarcted myocardium. Furthermore, infarction size was smaller in infarcted-treated (7.0±0.5%) compared with infarcted-controls (13.2±1.6%, p<0.05). Histopathology showed lack of hypertrophy in myocytes in peri-infarcted and remote myocardium and formation of islands/peninsulas of myocytes in infarcted-treated, but not in infarcted-controls. Conclusion: Plasmid HGF-gene caused near complete recovery of ejection fraction and improved radial and circumferential strain of remote, peri-infarcted and infarcted regions within 50 days. These beneficial effects may be explained by the combined effects of a speedy and significant infarct resorption and island/peninsulas of hypertrophied myocytes within the infarcted territory, but not by compensatory hypertrophy. The combined use of cine and tagging MR imaging provides valuable information on the efficacy of gene therapy.