Abstract Background Although the presence of thrombus in patients with ST-elevation myocardial infarction (STEMI) has been linked to adverse outcomes, routine thrombus aspiration has not been proven effective. A potential explanation is that these patients should be risk-stratified. Traditional clinical, laboratory and angiographic parameters used in clinical trials have been proven inadequate to classify patients. Aspirated thrombotic material characteristics might be an additional important parameter that has not yet been addressed. In this report, we aim to describe a methodological analysis of thrombus aspirated from coronary arteries during primary PCI using micro-Computed Τomography (micro-CT). These data will be combined with traditional factors to develop a risk-stratification system with high discriminative power for these patients. Methods Eighty-seven patients with STEMI undergoing thrombus aspiration in AHEPA University Hospital, Greece, will be enrolled in the study. The first patient was enrolled in June 2018. After being aspirated, thrombi are preserved in formalin and their volume and density are calculated with micro-CT. Micro-CT allows us to create 3D models of thrombi from a series of x-ray projection images. These models are further analyzed to find the volume and density of extracted thrombi and to assess potential differences in their structure. Association of these variables with clinical parameters and angiographic outcomes will be explored. Discussion QUEST-STEMI is-to our knowledge-the first study of volumetric coronary thrombus assessment by micro-CT. This method could be used in larger, clinically-oriented trials to help stratify patients with thrombus burden according to their risk for adverse outcomes. Trial registration QUEST-STEMI trial ClinicalTrials.gov number: NCT03429608 Date of registration: February 12, 2018. The study was prospectively registered (registered prior to enrollment of the first participant).