Earlier studies have shown that 7-monohydroxyethylrutoside (monoHER), an antioxidant flavonoid, protects against doxorubicin-induced cardiotoxicity. In this study, we investigated potential sustained cardioprotective effects of monoHER in a model of ischemia-reperfusion (I/R) in mice. Ischemia was induced for 30 min by ligating the left anterior descending coronary artery. Afterwards, the ligature was removed and reperfusion was allowed for 6 or 24 h or 2 weeks. MonoHER (500 mg/kg) was given intraperitoneally (i.p.) one hour before ischemia. Treatment with monoHER significantly attenuated myocardial neutrophil influx both at 6 and 24 h after reperfusion by 77% and 76%, respectively. Infarct size was also significantly reduced, 24 h and 2 weeks after reperfusion by 58% and 49%, respectively. Whereas ischemia-reperfusion had no influence on basal levels of cardiac contractility (+dp/dt), responses to dobutamine were blunted 24 h and 2 weeks after reperfusion. In mice treated with monoHER, cardiac contractility response was significantly restored. These results indicate that monoHER exerts a sustained cardioprotective effect on ischemia-reperfusion injury and prevents deterioration of cardiac contractility.