Postconditioning (PoC) with brief intermittent ischemia after myocardial reperfusion has been shown to lessen some elements of post-ischemic injury including arrhythmias and in some studies the size of myocardial infarction. We hypothesized that PoC could improve reflow to the risk zone after reperfusion. Anesthetized, open-chest rabbits were subjected to 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. In protocol 1 rabbits were randomly assigned to control (n=10, no further intervention after reperfusion) or to PoC consisting of four cycles of 30-second re-occlusions with 30 seconds of reperfusion in between starting at 30 seconds after the initial reperfusion (4 x 30/30, n=10). In protocol 2, rabbits were assigned to control (n=7) or received PoC consisting of four cycles of 60-second intervals of ischemia and reperfusion starting at 30 seconds after initial reperfusion (4 x 60/60, n=7). No reflow was determined by injecting thioflavine S, a fluorescent marker of capillary perfusion, risk zone by blue dye and infarct size by triphenyltetrazolium chloride. In protocol 1, there were no statistical differences in hemodynamics, ischemic risk zone or infarct size (35±6% of the risk zone PoC vs. 29±4% C, p = 0.38) between the groups. Similarly in protocol 2 PoC failed to reduce infarct size compared with control (45±4% of the risk zone PoC vs. 42±6% C, p = 0.75). There was a strong correlation in both protocols between the size of the necrotic zone and the portion of the necrotic zone that contained an area of no reflow. However postconditioning did not affect this relationship. PoC did not reduce infarct size in this model nor did it reduce the extent of the anatomic zone of no reflow, suggesting that this intervention may not impact post-reperfusion microvascular damage due to ischemia.