Background In the Effects of Postconditioning on Myocardial Reperfusion in Patients with ST-segment Elevation Myocardial Infarction (POST) trial, ischemic postconditioning failed to improve myocardial reperfusion. However, long-term effects of ischemic postconditioning on clinical outcomes are not known in patients with ST-segment elevation myocardial infarction. Methods A total of 700 patients undergoing primary percutaneous coronary intervention (PCI) were randomly assigned to the postconditioning group or the conventional primary PCI group in a 1:1 ratio. Postconditioning was performed immediately after restoration of coronary flow by balloon occlusion 4 times for 1 minute. Complete follow-up data for major clinical events at 1 year were available in 695 patients (99.3%), and analyses were done by the intention to treat principle. The primary outcome was a composite of death, myocardial infarction, severe heart failure, or stent thrombosis at 1 year. Results At 1 year, a composite of death, myocardial infarction, severe heart failure, or stent thrombosis occurred in 21 patients (6.1%) in the postconditioning group and 16 patients (4.6%) in the conventional PCI group (hazard ratio [HR] 1.32, 95% CI 0.69-2.53, P =.40). The risk of death (4.9% vs 3.7%, HR 1.32, 95% CI 0.64-2.71, P =.46), heart failure (2.6% vs 2.3%, HR 1.13, 95% CI 0.44-2.94, P =.80), and stent thrombosis (2.3% vs 1.7%, HR 1.34, 95% CI 0.46-3.85, P =.59) did not differ significantly between the 2 groups. Conclusions Ischemic postconditioning does not seem to improve the 1-year clinical outcomes in patients with ST-segment elevation myocardial infarction undergoing primary PCI.