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Purpose: ln-stent restenosis has been decreasing through the introduction of drug-eluting stents (DES). On the other hand, adverse events such as very late stent thrombosis (VLST) and late catch-up phenomenon can occur especially with sirolimus-eluting stents (SES, first-generation DES) in long-term follow-up. However, the precise mechanisms underlying VLST have not been well investigated in vivo. Methods and results: From 2004 to 2010, 2034 SES were implanted in 1656 patients and caused eight VLST (0.48% per patient) at Fukuoka Tokushukai Medical Center. Of these, serial intravascular ultrasound (IVUS) images (post-stent implantation and at the time of VLST onset) were obtained from three patients with VLST. Comparing them with eight control patients with SES implanted, the vascular reactivity of VLST patients was analyzed. Eight VLST happened 50 ± 15 months after stent implantation and three of the eight patients with VLST had not taken aspirin daily. There were no differences in minimum stent area, maximum external elastic membrane (EEM) area, and stent edge (distal and proximal) EEM area in post-procedural IVUS images. Compared with the control group patients, ?EEM area (10.6 ± 3.4 mm² vs. 1.7 ± 1.9 mm², p = 0.01) and vessel expansion ratio (185.6 ± 40.3% vs. 112.0 ± 12.1%, p = 0.01) were significantly greater in the VLST group based on the greater peri-stent plaque expansion (262.1 ± 72.8% vs. 118.7 ± 21.2%, p = 0.01). Conclusion: Our serial IVUS study showed that the vascular positive remodeling after SES implantation is one of the most probable morphological mechanisms for VLST development. [ABSTRACT FROM AUTHOR]