Background: No-reflow is considered a major percutaneous coronary intervention complication, especially in primary PCI. A variety of medications have been studied for no-reflow treatment, including intracoronary nitrates, verapamil, adenosine, glycoprotein IIb/IIIa inhibitors, and epinephrine. Glycoprotein IIb/IIIa inhibitors and epinephrine are the two most promising agents for the treatment of no-reflow. Aim of work: evaluating epinephrine and glycoprotein IIb/IIIa inhibitors efficacy in treating no-reflow through local distal intracoronary injection in comparison to traditional intracoronary administration in the guiding catheter. Subjects and methods: 30 patients undergoing PCI complicated by no-reflow phenomenon. Patients were randomized to either group I where they were treated by local distal intracoronary injection of GP IIb/IIIa inhibitor and epinephrine or to group II where they received the same medications via the traditional intracoronary injection. Primary outcomes were TIMI flow, corrected TIMI frame count and TMPG, and major adverse cardiac events within 48 hours was the secondary outcome. Results: Group I had significantly superior angiographic outcomes than group II. As regards TIMI II-III flow, 86.7% of patients achieved it in versus 53.3% in group II, CTFC was 8.2versus 9.9, and in group I, 80% of patients achieved TMPG II-III, compared to 46.7 % in group II. MACE was insignificantly different between both groups. Diabetes mellitus was found to be the only predictor to be negatively associated with TIMI flow. Conclusion: Distal coronary artery local injection of a combination of GP IIb/IIIa inhibitors and epinephrine achieved superior angiographic outcomes in the treatment of refractory no-reflow in comparison with traditional intracoronary administration of the same medications.