Abstract Background. Infarct size can be reduced by β-blockade in acute myocardial ischemia. However it is unknown whether myocardial salvage is still effective when β-blockade is limited to reperfusion. Methods. After initiation of cardiopulmonary bypass, 20 dogs were submitted to 2 hours of regional left ventricular ischemia, followed by 2 hours of reperfusion. In 11 dogs β-blockade was started with the onset of reperfusion (esmolol group). The remaining dogs received no treatment (control, n = 9). Infarct size was determined by tetrazolium chloride staining. Myocardial water content (MWC) and ultrastructural damage (electronmicroscopy) were determined from transmural biopsies. Results. Infarct size was significantly smaller in the esmolol group compared with control (49% versus 68%, p < 0.05). After 2 hours ischemia there was no difference in MWC between groups, whereas after 2 hours reperfusion MWC of ischemic myocardium was significantly lower in the esmolol group than in the control ( p < 0.05). Ultrastructural changes were typical for ischemia-reperfusion injury in both groups. Conclusions. β-Blockade may be cardioprotective during reperfusion through various mechanisms and may enhance myocardial salvage, even when treatment is initiated as late as with the onset of reperfusion.