Objectives: We sought to assess whether manual thrombus aspiration could reduce infarct size in patients with acute ST-elevation myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI). The efficacy of manual thrombus aspiration during primary PCI for acute MI remains controversial. Methods and Results: Between April 2009 and Mar 2011, 86 consecutive patients presenting with first acute STEMI (Killip���II) within 12 hours after the symptom onset were randomized to manual thrombus aspiration (group I, N=44) or conventional PCI without thrombus aspiration (group II, N=42). The use of glycoprotein IIb/IIIa inhibitor (GPI) was left to the discretion of the operator. All patients received aspirin 300 mg and clopidogrel 600 mg before PCI and underwent delayed enhancement (DE) multi-detector computed tomography (MDCT) immediately after PCI without injection of an additional contrast media for assessment of infarct size, determined as the total volume of myocardium showing DE. DE MDCT was repeated at 2 months after PCI. The primary endpoint was infarct size reduction at 2 months. Baseline clinical characteristics and angiographic findings were similar between the 2 groups. There were no differences between group I and II in symptom-to-door time (204짹205 min vs. 217짹168 min), door-to-balloon time (70짹42 min vs. 69짹25 min), PCI-to-MDCT time (17짹15 min vs. 13짹6 min), Pre-PCI TIMI 0/1, post-PCI TIMI 3, or the use of GPI. Markers of myocardial reperfusion showed better outcome in group I but without statistical difference: ST-resolution rate >70% (74% vs. 65%), myocardial blush grade 3 (88% vs. 68%), and corrected TIMI frame count <28 (31% vs. 24%). Initial infarct size determined by DE MDCT and left ventricular ejection fraction (LVEF) by 2-dimensional echocardiography were similar between group I and II (17짹18 mL vs. 22짹23 mL and 58짹11% vs. 55짹10%, respectively). At 2 months, there was no difference in infarct size and left ventricular ejection fraction between the groups: 14짹10 mL vs. 17짹12 mL and 62짹12% vs. 60짹2%, respectively. No adverse cardiac events occurred in either group during the 2-month clinical follow-up. Conclusions: Manual thrombus aspiration was not associated with reduction in infarct size in patients with acute ST-elevation MI receiving timely reperfusion therapy.