Abstract Rational The occurrence of stent thrombosis (ST) is a rare event, but it remains one of the most catastrophic complications following percutaneous coronary intervention (PCI). Coronary angiography has limited value in differentiating the causative factors responsible for ST. Technical resolutions We report a case of a 78-year-old male, hypertensive and dyslipidemic who underwent PCI with stenting of the mid left anterior descending artery (LAD) due to chronic coronary syndrome (CCD) two years before. He was admitted to our emergency department for syncopal episode occurred at rest followed by chest pain radiating to the left arm and to the neck. At the time of admission, his electrocardiogram showed diffuse ST-segment elevation in V2-V6 and DI-aVL, therefore patient was urgently sent to the cath lab. Coronary angiography showed LAD occlusion at the proximal edge of the previously implanted stent with TIMI flow grade 0 and TIMI thrombus grade 5. Multiple thrombus aspiration passes were performed with distal flow restoration, followed by intracoronary abciximab administration. After additional thrombus aspiration passes, ST-segment resolution was observed and chest pain improved significantly. OCT imaging of mid-to-proximal LAD was then performed to better characterize the cause of thrombosis. OCT revealed in stent-thrombosis with mixed thrombus (6 mm length, arc >270°) associated with major stent malapposition (maximum malapposition distance: 1.3 mm) at the proximal edge of the previous implanted stent, without evidence of neoatherosclerosis and/or residual disease with unstable features at the stent edges. Additional thrombus aspiration was performed, further reducing the thrombotic burden. As te patient was hemodynamically stable and asymptomatic, with TIMI flow grade 3 at coronary angiography, we decided to start dual antiplatelet therapy (ASA+ticagrelor) plus continuous heparin i.v. infusion, and to defer PCI, planning a control coronary angiography after 72 hours. After 72 hours, OCT revealed almost complete thrombus resolution, and guided PCI with a 4.0/8 mm everolimus-eluting stent in overlap with the previously implanted stent, postdilated with a 4.5 semi-compliant balloon at 18 atm. Revascularization was completed with an OCT-guided PCI of the proximal left circumflex during the same procedure. Clinical implications Our case demonstrates the utility of OCT in determining thrombus burden and assessing the causes of late stent failure, guiding PCI. In this case, OCT was useful as diagnostic tool to identify the mechanism underlying the very-late ST, and as guidance for treatment. It enabled to exclude neoatherosclerosis and/or unstable plaques at stent edges, leaving us more confident to defer PCI after 72 h of antithrombotic therapy. Perspectives The occurrence of ST is rare, but it remains one of the most catastrophic complications following PCI. Coronary angiography has limited value in differentiating the causative factors responsible for ST, while OCT allows to detect and characterize the causes of stent thrombosis (i.e., evaluate thrombus burden, presence of neoatherosclerosis, stent malapposition/underxpansion, uncovred stent struts, significant disease and/or unstable plaques at the stent edges, etc.). A better understanding of the pathophysiological mechanism underlying ST is an important clinical need. The increasing availability of high-resolution intravascular imaging techniques such as OCT provides new opportunities for tailoring treatment strategy and guiding PCI.