Age-related changes in the mouse heart after ischemia-reperfusion have not been well characterized. To test the hypothesis that advanced age was associated with increased susceptibility to myocardial injury after ischemia/reperfusion, we studied the hearts of young adult and old mice. In young adult (6-8 months) and aged (22-24 months) C57 BL/6 mice, we performed left anterior descending coronary artery ligation and subjected the hearts to 45 min of ischemia followed by varying periods of reperfusion of 15 min, 1 h, 4 h, and 24 h. We found that there was a significant age difference in the size of the infarct between the young adult and old hearts. There was also greater damage in the old hearts in terms of contraction band necrosis, myofiber tears, DNA fragmentation, and mitochondrial disruption. Thus, the old heart is more susceptible to injury after ischemia-reperfusion. This may be partly due to an age-associated decrease in coronary circulation and collateral flow, as well as other factors.