Introduction: Stent thrombosis after drug-eluting stent (DES) was associated with significant morbidity and mortality. Intravascular ultrasound (IVUS) studies have suggested that suboptimal stent deployment can cause stent thrombosis. We evaluated the effect of IVUS-guided primary percutaneous coronary intervention (PPCI) in patients with ST segment elevation myocardial infarct (STEMI) on stent thrombosis of DES. Methods: We reviewed 395 patients who underwent PPCI with DES due to STEMI in our institution from January 2003 to December 2008. Difference of major adverse cardiac event (MACE) consisted with death, myocardial infarct, target lesion revascularization and target vessel revascularization and early stent thrombosis (ST) 1 month after PPCI was compared between patients with angiographic guided PCI and IVUS-guided PCI group. Early ST means acute and subacute ST. Results: 171 (43.3%) patients underwent PPCI due to STEMI. Men were 74.3% in IVUS-guided group and 62.1% in angiographic guided group (p = 0.01). There was no difference in killip class and culprit lesion. There was no difference in history of diabetes, hypertension, previous PCI, cerebrovascular attack and dyslipidemia. But history of previous MI and smoking were more common in IVUS group (MI: 12.9% vs 6.3%, p = 0.024; Smoking: 74.9% vs 53.1%, p < 0.01). There was no difference in aspirin, clopidogrel and statin use. Higher cilostazol use in angiography group and higher glycoprotein IIb/IIIa (GP2b/3a) receptor inhibitor use in IVUS group were seen (cilostazol: 8.2% vs 17.0%, p = 0.011; GP2b/3a inhibitor: 15.8% vs 3.6%, p < 0.01). There was no difference in disease extent, initial TIMI flow grade. Most patients were implanted sirolimus- (SE), paclitaxel- (PES) and zotarolimus-eluting stent (ZES) (SES: 23.4% vs 60.3%; PES: 12.9% vs 17.9%; ZES: 19.9% vs 14.3%; p < 0.01). There was no difference in lesion length and binary post minimal luminal diameter. There was no difference in MACE 1 month after PPCI but stent thrombosis was significantly lower in IVUS group (0% vs 2.7%, p = 0.039). 5 of 6 ST were subacute ST and the other was acute ST. All of ST were probable ST by ARC definition. Use of IVUS showed statistically significance after adjusting history of MI, use of cilostazol and GP2b/3a inhibitor and variety of DES by using ANCOVA (p = 0.02). Conclusion: IVUS-guided PPCI in patient with STEMI could reduce early stent thrombosis of DES independent of history of MI, use of cilostazol and GP2b/3a inhibitor and variety of DES.