AIMS Subacute, late, and very late stent thrombosis (ST) may occur after stent implantation, but they are characterised by different underlying pathophysiological mechanisms. We sought to appraise differences between subacute and late/very late ST at the thrombus site by optical coherence tomography (OCT). The Mechanism Of Stent Thrombosis (MOST) study was a prospective multicentre non-randomised registry which enrolled six subacute ST and six controls (subacute ST study), and 17 late/very late ST and 17 controls (late/very late ST study). METHODS AND RESULTS Patients with subacute ST had a minimum stent area at the thrombus site of 2.1 mm² (1st-3rd quartile 1.3-4.5) vs. 2.9 mm² (2.4-5.0) in the matched control (p=0.05). Uncovered struts were 26.2% (16.5-35.9) vs. 13.9% (8.9-18.9), p=0.001. Malapposed struts were 18.8% (13.1-24.5) vs. 15.2% (12.8-17.6), p=0.001. In patients with late/very late ST, uncovered struts were 23.6% (13.9-33.3) vs. 5.2% (0.5-10.2), p=0.001. Malapposed struts were 12.1% (6.4-17.8) vs. 2.8% (0.4-5.2), p=0.001, and maximum malapposition distance was 0.45 mm (0.32-0.62) vs. 0.12 mm (0-0.25), p=0.01. Notably, all patients with ST had previously discontinued dual antiplatelet therapy (n=14) or showed high residual platelet reactivity on clopidogrel therapy. CONCLUSIONS Subacute ST had a significant stent underexpansion while late/very late ST had a greater stent strut malapposition distance at the thrombus site. These findings explain how procedure-related complications and vessel remodelling have a specific impact on the segment characterised by thrombus. High platelet reactivity also seems a necessary cofactor for both subacute and late/very late ST. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov unique identifier NCT01410539.