In patients with acute myocardial infarction (AMI), the off-hour presentation is one of the major determinants of door-to-balloon delay. Moreover, the nighttime presentation is associated with increased mortality after primary coronary intervention (PCI). The prompt starting of a therapy able to start recanalization of the infarct-related artery before intervention might improve the results of off-hour primary PCI. We compared the outcome of 212 consecutive patients with AMI undergoing either direct or facilitated PCI according to the hour of presentation. Patients arriving off-hours were pretreated with alteplase (20 mg) and abciximab and underwent facilitated PCI. Patients presenting on-hours underwent direct PCI. A basal Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 was observed in 1.0% of patients undergoing direct PCI and in 44% of patients undergoing facilitated PCI (P = 0.001). More patients starting PCI with a TIMI 3 flow achieved a postinterventional fast TIMI frame count (72.0% vs. 38.8% direct PCI group vs. 34.9% facilitated PCI group with basal TIMI 0-2; P = 0.001) and a TIMI perfusion grade 3 (66.0% vs. 38.8% direct PCI group vs. 39.7% facilitated PCI group with basal TIMI 0-2; P = 0.004). Preinterventional TIMI flow grade 3 was associated with a higher gain in left ventricular ejection fraction at 1 month (10.9% +/- 6.4% vs. 7.0% +/- 9.6% direct PCI group vs. 6.1% +/- 6.0% facilitated PCI group with basal TIMI 0-2; P = 0.005). No significant difference was observed in major bleedings, although there was a trend toward a higher risk in the facilitated PCI group. Patients in the facilitated PCI group achieving a basal TIMI 3 flow showed improved myocardial reperfusion and better left ventricular function recovery. Bleeding complications associated with combination therapy remained an important concern.