Very late thrombosis in an implanted bare-metal stent is a very uncommon event outside the context of brachytherapy and few data about its pathophysiology are available. We performed an intravascular ultrasound study during primary angioplasty in five patients with very late bare-metal stent thrombosis and carried out a histological analysis of the material removed by manual thrombectomy. The mean time from the index procedure was 7 ± 4 years. Intravascular ultrasound findings were: calcified atherosclerosis with in-stent plaque rupture, complex plaque in the distal segment of the stent, in-stent neointimal proliferation associated with underexpansion, and severe in-stent proliferation. Histological findings were consistent with the intravascular ultrasound images: recent thrombus with areas of old thrombosis in all cases and remnant atheromatous plaque and endothelium. Consequently, in-stent or distal stent atherosclerosis progression and progressive neointimal proliferation were the likely pathophysiological mechanisms.