The aim of the present study was to compare 600- and 300-mg clopidogrel loading doses in patients with ST-segment elevation myocardial infarctions who underwent primary percutaneous coronary intervention (PCI). Two hundred fifty-five consecutive patients presenting with ST-segment elevation myocardial infarctions who underwent primary PCI were enrolled. Patients were divided into 2 groups on the basis of the loading dose of clopidogrel received before the procedure (600 vs 300 mg). Procedural angiographic end points and 1-year major adverse cardiac events were compared between the 2 groups. Major adverse cardiac events were defined as death, nonfatal myocardial infarction, and target vessel revascularization. There were no significant differences in baseline clinical and angiographic features between the 2 groups: 157 (62%) in the clopidogrel 600 mg group and 98 (38%) in the 300 mg group. Patients receiving 600-mg loading dose of clopidogrel showed a significantly lower incidence of post-PCI myocardial blush grade 0 or 1 (odds ratio 0.64, 95% confidence interval 0.43 to 0.96, p = 0.03) and significantly less common no-reflow phenomenon (odds ratio 0.38, 95% confidence interval 0.15 to 0.98, p = 0.04) compared to those in the 300-mg group. Propensity-adjusted Cox analysis showed significantly higher survival free of major adverse cardiac events in patients receiving 600-mg loading dose of clopidogrel compared to those receiving the lower dose (hazard ratio 0.57, 95% confidence interval 0.33 to 0.98, p = 0.04). In conclusion, a 600-mg loading dose of clopidogrel is associated with improvements in procedural angiographic end points and 1-year clinical outcomes in patients with ST-segment elevation myocardial infarction who undergo primary PCI compared to a 300-mg dose.