Purpose Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardiac events after coronary intervention. As compared with the conventional 300-mg dose, pretreatment with a 600-mg loading dose of clopidogrel significantly reduced periprocedural myocardial infarction (MI) in patients undergoing percutaneous coronary intervention (PCI). We investigated that the advantage of the 600-mg dose in inhibiting platelet aggregation more rapidly than the 300-mg dose may actually have special value for STEMI patients. Methods From 2004 to 2005, a total of 165 patients with STEMI underwent primary percutaneous coronary stenting. A 600-mg (n=67) or 300-mg (n=98) loading regimen of clopidogrel was given before the procedure. We followed all patients clinically for 30 days after coronary intervention. The primary end point was the 30-day occurrence of death, myocardial infarction, urgent revascularization, or stroke. Results The primary end point occurred in 3% (2/67) of patients in the high dose versus 11% (11/98) of those in the conventional loading dose group (p=0.044) and was due entirely to urgent revascularization (p=0.021). Death, recurrent MI, and stroke were lower in patients treated with the high dose of clopidogrel compared with conventional dose without significance. Safety end points were similar in the 2 groups. Conclusion Pretreatment with a 600-mg loading dose of clopidogrel before the procedure is safe and, as compared with the conventional 300-mg, significantly reduced urgent revascularization in patients with primary PCI.