Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Isfahan University of Medical Sciences, Isfahan, Iran. Introduction Todays, acute ST-segment elevation myocardial infarction (STEMI) is considered as a most important component of acute coronary syndrome. In this regards, reperfusion therapy with percutaneous coronary intervention (PCI) is the most effective treatment for establishing coronary blood flow; which despite reperfusion of ischemic myocardium, it can also induce secondary injury as myocardial ischemia-reperfusion injury. The generation of reactive oxygen species by activation of xanthine oxidase (XO) enzymatic system is one of the major causes of ischemia-reperfusion injury in the ischemic myocardium and allopurinol, a XO inhibitor, has an inhibitory role on free radical productions in STEMI patients. Purpose In this study, we aimed to assess impact of allopurinol pre-treatment on revascularization outcomes, according to Thrombolysis in Myocardial Infarction (TIMI) flow and ST segment elevation recovery as well as clinical finding and major cardiac events incidence in STEMI patients underwent emergency PCI. Methods In this randomized double blind clinical trial, we enrolled 90 patients with acute STEMI in two equal groups. Allopurinol group received 600 mg allopurinol loading dose before the emergency PCI and the control group received the same shape medication as a placebo. Both groups also received the standard pretreatment protocol for PCI in acute STEMI setting. TIMI flow, ECG changes, Troponin level and major cardiac events (MACE) occurrence including death, myocardial infarction and ischemic stroke after 1 month follow up were assessed. In case group, allopurinol 100 mg daily and matched placebo pill for control group was continued for one month in addition to standard medications. Results Finally, 81 patients with acute STEMI has completed the study. The mean age of study population was 59.52 (11.31) and 61.3 (9.25) in case and control groups respectively (p = 0.49). Troponin level 48 hour after the PCI had not significant difference between the groups (p = 0.25). ECG ST-elevation regression also had not significant difference between the groups [75.0%1 vs 67.10% in case and control groups, respectively (p = 0.21)]. TIMI flow had improved in allopurinol group rather than placebo (p = 0.02). PCI success rate was 78.6% and 61.5% in allopurinol and control group respectively (p = 0.09). MACE and other clinically outcomes in follow up period were similar between groups (p > 0.05). Conclusions This study indicated that allopurinol pre-treatment loading dose could improve minimally revascularization outcomes based on TIMI flow in the patients undergoing primary or rescue PCI in acute STEMI setting.