Abstract Background Although very late stent thrombosis (VLST) remains an important concern, the underlying etiology and clinical characteristics are not fully elucidated in Japanese patients who daily undergo intravascular imaging-guided percutaneous coronary intervention (PCI). Objectives The aim of this study was to explore the mechanisms of VLST in bare metal stents (BMSs) and drug eluting stents (DESs) in Japanese patients. Methods We identified 50 VLST lesions (BMS [n=16], 1ST generation DES [n=14], newer generation DES [n=20]) in patients managed in our institutes. The underlying mechanism of VLST was assessed by optical coherence tomography (OCT) and the major etiology of each lesion was determined. Results The median duration following stent implantation was 10 (range 1–20) years. The most frequent etiology of VLST was neoatherosclerotic rupture (44%) followed by neointimal erosion (24%). Edge disease (10%) and evagination (10%) were similarly observed. Malapposition (8%) was mostly acquired late by going back to the index procedure. Uncovered strut (2%) and in-stent calcified nodule (2%) were the least frequent etiologies. Regardless of etiology, signs of neoatherosclerosis were present in most (82%) lesions. Most patients received single (68%) or dual (8%) antiplatelet therapy or oral anticoagulation alone (4%), whereas considerable proportion of patients stopped any medication (20%). Regarding the treatment strategy, drug-coated balloon was the most frequent strategy (56%), followed by newer DES implantation (34%). Conclusion The mechanisms underlying VLST in Japanese patients were unique, with neoathersclerotic rupture and neointimal erosion accounting for two-thirds of cases of VLST. In these patients, biological responses seemed to be more relevant rather than index procedure-related factors.