SUMMARYObjectives: To elucidate the efficacy and safety of pharmacoinvasive therapy by using prourokinase (prouk) in patients with ST-segment elevation myocardial infarction (STEMI). Background: Patients with STEMI often have long percutaneous coronary intervention (PCI)-related delays due to various reasons, which are associated with poor outcomes. Methods: A randomized study which enrolled patients from four centers in China was conducted. Patients were randomly assigned to accept routine primary PCI or prouk-PCI. The primary end points were the angiographic parameters, including thrombolysis in myocardial infarction (TIMI) flow grade, TIMI frame count, and myocardial blush grade. Secondary endpoints were incidence of major adverse cardiac events (MACE, defined as death from all causes, reinfarction, revascularization, or rehospitalization due to new or worsening congestive heart failure) at 30 days and 1 year. Results: One hundred and ninety-seven eligible patients were enrolled, of whom 100 were randomized to the prouk-PCI group. Significantly more patients in the prouk-PCI group than in the PCI group had an opened infarct-related artery on arrival in the catheterization laboratory (48% vs. 21%, P = 0.0002) and better TIMI frame count after PCI (33 AE 6 vs. 40 AE 10, P < 0.001). At 1-year follow-up, there was a trend that patients in the prouk-PCI group had less chances to have MACE (7.0% vs. 12.6%, P = 0.235) or be readmitted to hospital due to new or worsening congestive heart failure (1.0% vs. 4.1%, P = 0.209). Conclusion: A strategy of emergent PCI preceded by fibrinolysis with prouk results in a better myocardial perfusion in infarct-related artery compared with primary PCI alone in patients with STEMI and long PCI-related delay.Primary percutaneous coronary intervention (PCI) is an effective treatment for ST-segment elevation myocardial infarction (STEMI) when it can be performed rapidly [1]. However, this procedure may not completely prevent further myocardial damage due to reperfusion injury and distal embolization [2]. More importantly, even in the hospital with primary PCI capability, patients with STEMI often have long PCI-related delays due to various reasons, which are associated with poorer outcomes [3]. In those patients, the appropriate and timely use of reperfusion therapy is likely more important than the choice of reperfusion methods. Indeed, American College of Cardiology/American Heart Association (ACC/AHA) guidelines recognize that one reperfusion approach is not superior for all patients, in all clinical settings, at all times of day [4]. The use of facilitated PCI was shown to be detrimental compared with primary PCI, with increased ischemic and bleeding events, and a trend toward excess mortality [5,6]. Conversely, among high-risk STEMI patients, the treatment with fibrinolysis and transferred for PCI within 6 h after fibrinolysis was associated with significantly fewer ischemic complications than that in standard treatment [7]. Tissue plasminogen activator (t-PA) is the commonly use...