BACKGROUND: Treatment of significant coronary artery disease with primary percutaneous coronary intervention (PCI) seems better than angioplasty balloon; because the incidence of restenosis is lower in this method, however, a serious complication of PCI is stent thrombosis which would lead to repeated myocardial infarction (MI) and increase the mortality and morbidity. One of the frequent medications which is used to prevent from stent thrombosis is clopidogrel, but, stent thrombosis was seen in many of the patients despite given the conventional dosage of this drug. This study aimed to evaluate the effect of doubling the maintenance dose of clopidogrel to prevent from early stent thrombosis, MI and mortality rate. METHODS: This was a clinical trial study which was done in Shahid Chamran Hospital in winter 2010 in Isfahan, Iran. A total of 400 patients with PCI were prospectively followed-up for 30 days. All the patients were randomly allocated into two groups. The control group received a maintenance dose of 75 mg clopidogrel while the case group received 150 mg clopidogrel after the initial dosage of 600 mg for 30 days after the PCI. The incidence of primary outcome such as total mortality was recorded during the study. RESULTS: Early stent thrombosis was observed in 4 patients (1%) (One subject in the control group and 3 in the case group) during the first 30 days after PCI, but the difference was not significant between the two groups (p = 0.62). Mortality due to stent thrombosis occurred in 2 patients in the case group which showed no significant difference in this group (p = 0.5). In addition, MI occurred in 2 patients (1 in each group) which also showed no significant difference between the two groups (p = 1). Drug complication such as major bleeding had no significant difference between the two groups (p = 0.9). CONCLUSION: The present study showed that doubling dose of clopidogrel could not reduce the incidence of early stent thrombosis, mortality and myocardial infarction in comparison with conventional dosage; therefore it is recommended that more studies be done in Iranian and Asian race for clinical decision-making to prevent form stent thrombosis using high dose of clopidogrel.Keywords: Primary coronary intervention, Early stent thrombosis, Clopidogrel, Coronary stenting.