The MRL/MpJ mouse strain has been reported to recover after right ventricular cryoinjury without scar formation or evidence of ventricular dysfunction, suggesting that this mouse strain harbors genetic traits that confer the capacity for adult myocardium to regenerate. We therefore sought to assess the capacity of adult MRL myocardium to regenerate in a left ventricular ischemia-reperfusion model of myocardial infarction, which more closely recapitulates injury that occurs in human disease. MRL (n = 13) and control C57/Bl6 (n = 12) mice underwent transient occlusion of the left anterior descending coronary artery. After 10 weeks, MRL and C57Bl/6 mice were euthanized and the extent of infarcted myocardium quantified with (2,3,5)-triphenyltetrazolium chloride and trichrome staining. There was no evidence of resistance to cardiac injury or of reduced scar formation in the MRL mice compared to C57/Bl6 controls. Myocardial infarct size (percentage of total heart weight ± SEM) did not significantly differ between MRL and C57/Bl6 controls (18.9 ± 1.8% for MRL vs. 15.7 + 1.3% for C57/Bl6, p = 0.20). Thickness of the infarcted anterior LV wall at the mid-papillary level normalized to body weight was not significantly different between the two groups (0.017 + 0.003 mm/mg for MRL and 0.017 + 0.002 mm/mg for C57/BL6, p = 0.91). Trichrome staining showed intense scar formation in both C57/BL6 and MRL hearts. We conclude that there appears to be no effect of the MRL genetic background on resistance to myocardial infarction in mice.