Background No randomized trial has been performed to compare the efficacy of an intracoronary bolus of tirofiban versus urokinase during primary percutaneous coronary intervention (PCI).We investigated whether the effects of adjunctive therapy with an intracoronary bolus of urokinase was noninferior to the effects of an intracoronary bolus of tirofiban in patients with ST-elevation myocardial infarction (STEMI) undergoing PCI.Methods A total of 490 patients with acute STEMI undergoing primary PCI were randomized to an intracoronary bolus of tirofiban (10 μg/kg; n=247) or urokinase (250 kU/20 ml; n=243).Serum levels of P-selectin,von Willebrand factor (vWF),CD40 ligand (CD40L),and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary drug administration.The primary endpoint was the rate of complete (＞70％) ST-segment resolution (STR) at 90 minutes after intervention,and the noninferiority margin was set to 15％.Results In the intention-to-treat analysis,complete STR was achieved in 54.4％ of patients treated with an intracoronary bolus of urokinase and in 60.6％ of those treated with an intracoronary bolus of tirofiban (adjusted difference:-7.0％;95％ confidence interval:-15.7％ to 1.8％).The corrected TIMI frame count of the infarct-related artery was lower,left ventricular ejection fraction was higher,and the 6-month major adverse cardiac event-free survival tended to be better in the intracoronary tirofiban group.An intracoronary bolus of tirofiban resulted in lower levels of P-selectin,vWF,CD40L,and SAA in the coronary sinus compared with an intracoronary bolus of urokinase after primary PCI (P＜0.05).Conclusions An intracoronary bolus of urokinase as an adjunct to primary PCI for acute STEMI is not equally effective to an intracoronary bolus of tirofiban with respect to improvement in myocardial reperfusion assessed by STR.This may be caused by less reduction in coronary circulatory platelet activation and inflammation.