Postconditioning (PosC), which is a brief period of ischemia performed at the time of reperfusion therapy, reduces the infarct size in animal models. We aim to evaluate the impact of PosC in patients with ST-elevation acute myocardial infarction (STEMI). Between January 2008 and August 2009, 37 STEMI patients received PosC. The control group comprised 42 age- and sex-matched patients diagnosed with STEMI in 2007–2008. In the PosC group, we applied four cycles of 30-s balloon inflation and 30-s balloon deflation within 3 min after thrombectomy, and implanted the stent after PosC. In the control group, we directly implanted the stent after thrombectomy. The number of patients with myocardial blush grade 2 or 3 after the procedure was higher in the PosC group than in the control group (65 vs. 43%, p = 0.04). The ST-segment resolution >50% was greater in the PosC group compared to the control group (81 vs. 57%, p = 0.02). Serial changes of creatine kinase and creatine kinase myocardial fraction after reperfusion were significantly lower in the PosC group than in the control group. In conclusion, PosC is a safe and feasible strategy that might preserve myocardial perfusion and reduce the infarct size in patients with STEMI.