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Left ventricular (LV) remodeling after acute myocardial infarction (AMI) is associated with a poor prognosis and an impaired quality of life. We have shown earlier that low-energy extracorporeal cardiac shock wave (SW) therapy improves chronic myocardial ischemia in pigs and humans and also ameliorates LV remodeling in a pig model of AMI induced by permanent coronary ligation. However, in the current clinical setting, most of the patients with AMI receive reperfusion therapy. Thus, in this study we examined whether our SW therapy also ameliorates LV remodeling after myocardial ischemia–reperfusion (I/R) injury in pigs in vivo.Pigs were subjected to a 90-min ischemia and reperfusion using a balloon catheter and were randomly assigned to two groups with or without SW therapy to the ischemic border zone (0.09 mJ/mm2, 200 pulses/spot, 9 spots/animal, three times in the first week) (n=15 each).Four weeks after I/R, compared with the control group, the SW group showed significantly ameliorated LV remodeling in terms of LV enlargement (131±9 vs. 100±7 ml), reduced LV ejection fraction (28±2 vs. 36±3%), and elevated left ventricular end-diastolic pressure (11±2 vs. 4±1 mmHg) (all P<0.05, n=8 each). The SW group also showed significantly increased regional myocardial blood flow (−0.06±0.11 vs. 0.36±0.13 ml/min/g, P<0.05), capillary density (1.233±31 vs. 1.560±60/mm2, P<0.001), and endothelial nitric oxide synthase activity (0.24±0.03 vs. 0.41±0.05, P<0.05) in the ischemic border zone compared with the control group (n=7 each).These results indicate that our SW therapy is also effective in ameliorating LV remodeling after myocardial I/R injury in pigs in vivo.