No-reflow is a frequent event during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and it may affect cardiac prognosis. We evaluated the occurrence of no-reflow as a predictor of outcomes in patients who underwent PCI for AMI. We prospectively collected data from 599 consecutive patients who underwent stent-based PCI for ST-elevation AMI by identifying those with no-reflow (Thrombosis In Myocardial Infarction [TIMI] grade <3 flow at completion of the procedure) and analyzing their baseline characteristics and clinical outcomes. Patients with no-reflow (n = 40, 6.7%) were older (67 ± 13 vs 60 ± 13 years, p = 0.002) and had longer ischemic times (5.5 ± 3.7 vs 4.4 ± 3.0 hours, p = 0.04) with more TIMI grade 0/1 flow at presentation (90% vs 64%, p = 0.001). No-reflow occurred mostly (73%) after stenting and often required intra-aortic balloon pump counterpulsation (30% vs 4.3%, p <0.001). Peak creatine kinase level was higher in patients with no-reflow (2,700 ± 1,900 vs 2,000 ± 1,800, p = 0.03) and more often associated with moderate or severe left ventricular dysfunction (68% vs 45%, p = 0.006) and increased 6-month mortality (12.5% vs 4.3%, p = 0.04). By multivariate analysis, no-reflow was an independent predictor of long-term mortality (odds ratio 3.4, p = 0.02). In addition, renal failure (odds ratio 4.39, p = 0.0025) and preprocedure TIMI grade 0/1 flow (odds ratio 2.1, p = 0.003) were independent predictors of no-reflow. In conclusion, the association of no-reflow with longer ischemic time and worse initial TIMI flow may indicate the presence of highly organized thrombus burden with higher propensity for distal embolization. Regardless of its mechanism, no-reflow was an independent predictor of increased mortality.