Background: We assessed resolution of ST segment elevation after primary percutaneous coronary intervention (PCI) with the PercuSurge GuardWire (PSG) system for lesions with angiographic features suggesting large thrombus burden of the infarct-related artery (IRA). Methods: Between June 2002 and May 2003, we enrolled 30 patients with acute myocardial infarction that underwent primary PCI with angiographic features suggesting large thrombus burden of the IRA (abrupt end occlusive pattern, persistent dye stasis, reference diameter >4mm, floating thrombus, accumulated thrombus >5mm). Fourteen patients received primary PCI with the PSG system (PSG group) and sixteen patients received primary PCI without PSG system (control group). We compared angiographic results (TIMI flow, myocardial blush grade), > 50% resolution of ST segment elevation at 2 hours after reperfusion and in hospital major adverse cardiac events between the two groups. Results: Baseline clinical and angiographic characteristics were not significantly different between the two groups. Primary PCI with the PSG system was performed successfully in all patients. Significantly more Post PCI TIMI grade 3 flow and myocardial blush grade 3 were achieved in the PSG group compared with the control group (100 % vs. 69 %, p=0.022, 57 % vs. 6 %, p=0.004, respectively). Significantly more >50% resolution of ST-segment elevation was observed in the PSG group (79 % vs. 31 %, p=0.01). The incidences of in hospital major adverse cardiac events were lower in the PSG group than in the control group; two deaths and one recurrent myocardial infarction (0 % vs. 18.8 %, respectively p=0.044). Conclusion: Primary PCI with PercuSurge GuardWire system might improve coronary blood flow, microvascular circulation and in-hospital outcomes in patients with angiographic features suggesting large thrombus burden of the IRA.