The aim of this study was to understand the impact of attenuated plaque on distal embolization during stent implantation in patients with acute myocardial infarction (AMI). Attenuated plaques identified by grayscale intravascular ultrasound (IVUS) might predict transient deterioration in coronary flow and/or no-reflow during percutaneous coronary intervention (PCI). We analyzed clinical, angiographic, and IVUS data from 364 patients (n = 364 infarct-related arteries) enrolled in the randomized HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. No-reflow was final Thrombolysis In Myocardial Infarction (TIMI) flow grade ≤2 in the absence of mechanical obstruction. Attenuated plaque was hypoechoic or mixed atheroma with ultrasound attenuation without calcification. A mean attenuation score was created by measuring the angle of attenuation each 1 mm, scoring the angle as 1 to 4 (corresponding to <90°, 90° to 180°, 180° to 270°, or 270° to 360°, respectively), summing the scores, and normalizing for analysis length. Overall, 284 (78.0%) patients had attenuated plaques; no-reflow occurred in 37 (10.2%). Patients with no-reflow had a higher mean attenuation score (median [interquartile range] 2.2 [0.0 to 2.8] vs. 1.3 [0.7 to 1.8], p < 0.001), lower baseline left ventricular ejection fraction (52.8% [43.2% to 61.5%] vs. 61.4% [52.2% to 68.1%], p = 0.002), and more baseline angiographic thrombus (89.2% vs. 74.1%, p = 0.043) with no differences in post-PCI stent expansion versus patients without no-reflow. Multivariate analysis indicated that mean attenuation score was the strongest predictor of no-reflow. The mean attenuation score that best predicted no-reflow was ≥2 points (90° to 180°, sensitivity of 81.5%, and specificity of 80.5%). Attenuated plaque was present in three-quarters of patients with AMI. The amount of attenuated plaque strongly correlated with no-reflow; the larger the attenuated plaque, the greater the likelihood of no-reflow. (Dual Arm Factorial Randomized Trial in Patients w/ST Segment Elevation AMI to Compare the Results of Using Anticoagulation With Either Unfractionated Heparin + Routine GP IIb/IIIa Inhibition or Bivalirudin + Bail-out GP IIb/IIIa Inhibition; and Primary Angioplasty with stent implantation with Either a Slow Rate-release Paclitaxel-eluting Stent [TAXUS™] or Uncoated Bare Metal Stent [EXPRESS2™]; NCT00433966).