Background: The role of upstream high-dose statin therapy in patients undergoing primary percutaneous coronary intervention (PCI) has yet to be determined. We sought to assess whether high-dose statin loading could reduce infarct size in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary PCI. Methods: Between April 2009 and April 2010, a total of 34 statin-naive patients presenting with first acute STEMI (Killip class I or II) within 12 hours after the symptom onset were randomly assigned to rosuvastatin 40 mg loading before PCI followed by rosuvastatin 10-40 mg daily (group 1, N=17) or no statin loading before PCI followed by rosuvastatin 10-20 mg daily (group 2, N=17). All patients received 300 mg of aspirin and 600 mg of clopidogrel on admission. Immediately after PCI, the patients underwent delayed enhanced (DE) MDCT without injection of an additional contrast media to assess infarct size, determined as the total volume of myocardium showing DE. DE MDCT was repeated at 2 months after PCI and infarct size reduction was compared between the two groups. Results: Baseline clinical and angiographic characteristics were similar in both groups. There were no differences in ST-resolution rate, myocardial blush grade, corrected TIMI frame count and the use of glycoprotein IIb/IIa inhibitors, thrombus aspiration, and drug-eluting stents between the groups. Patients in group 1 and 2 had similar baseline low-density lipoprotein (LDL)-cholesterol level (118.3짹22.9 mg/dl vs. 119.1짹25.9 mg/dl, p=0.921), left ventricular ejection fraction (LVEF) (57.8짹7.7% vs. 58.0짹10.5%, p=0.938), and infarct size on MDCT (24.7짹15.4 ml vs. 21.4짹20.7 ml, p=0.599). At 2 months, there were no statistical differences in LDL-cholesterol level (65.7짹30.7 mg/dl vs. 77.7짹23.2 mg/dl, p=0.921), LVEF (56.3짹6.7% vs. 60.6짹8.4%, p=0.938), and infarct size on MDCT (20.7짹14.6 ml vs. 17.5짹11.4 ml, p=0.476). Infarct size reduction was similar (4.1짹7.7 ml vs. 4.0짹11.5 ml, p=0.979) and no death or MI was noted in either group at 2 months. Conclusion: This interim analysis failed to demonstrate a benefit of upstream high-dose statin therapy in infarct size reduction in patients with acute STEMI undergoing primary PCI. The completion of this study will help resolve this issue.