Aims: The aim of the trial was to examine the influence of ezetimibe on plaque morphology in patients with ST-segment Elevation Myocardial Infarction (STEMI)with respect to fibrous cap thickness (FCT)and arcs of lipid plaque, calcific plaque, and macrophages using Optical Coherence Tomography (OCT). Methods and results: In 87 statin naïve patients with STEMI treated with primary percutaneous intervention, a non-culprit study plaque in a non-infarct related coronary artery was assessed with OCT at baseline and after 12 months. Patients were treated with atorvastatin 80 mg and randomized (1:1)to ezetimibe 10 mg (n = 43)or placebo (n = 44). An increase in median FCT (ezetimibe 200 (140–260)μm to 240 (190–305)μm (p = 0.002)vs. placebo 205 (135–260)μm to 230 (180–270)μm (p < 0.001), between groups p = ns), a reduction in lipid arc (ezetimibe 1728.5 (1022.5–3904.7)° to 1164.5 (736.6–2580.1)° (p = 0.001)vs. placebo 1671.6 (978.3–2868.7)° to 1373.7 (791.2–2267.3)° (p = 0.019), between groups p = ns), and macrophage arc (ezetimibe 1730.3 (965.7–2984.4)° to 1324.8 (819.0–2819.7)° (p < 0.05)vs. placebo 1570.5 (794.7–3016.8)° to 1418.9 (584.1–2501.1)° (p < 0.01), between groups p = ns)were observed. Conclusion: Aggressive LDL-lowering resulted in changes in OCT assessed plaque composition by increased FCT thickness and a reduction in lipid content and macrophage infiltration. Addition of ezetimibe 10 mg to atorvastatin 80 mg resulted in further LDL reduction, but no additional change in plaque composition was found.