Even in the current drug-eluting stent (DES) era, percutaneous coronary intervention (PCI) for calcified coronary lesions when compared to non-calcified coronary lesions remains challenging, due to difficult device delivery, suboptimal stent expansion, and prolonged procedure time with more complications, and is associated with the increased risk of target lesion revascularization and stent thrombosis . A recent pathologic study has investigated the underlying mechanisms behind such events . A total of 134 lesions treated with newer-generation DES from 104 autopsy cases (85 Xience everolimus-eluting stent [EES] lesions and 29 Resolute zotarolimus-eluting stent lesions, 17 Element-EES lesions, and 3 Synergy-EES lesions) with duration of implant ≥30 days were histologically analyzed and classified into two groups according to the presence or absence of severe calcification in the stented lesions assessed by radiographs: severely calcified lesion (SC, n = 46) and non-severely calcified lesion (NC, n = 88). The prevalence of stent thrombosis in the SC group was significantly higher than that in the NC group (4 cases [9%] vs. 0 cases [0%], respectively, P = 0.01). The prevalence of restenosis was also numerically higher in SC compared to NC (8 cases [17%] vs. 6 cases [7%], respectively, P = 0.054). In the morphologic and morphometric analysis, SC was associated with higher incidence of uncovered strut per lesion (2.4 [interquartile range (IQR) 0.0–19.0] % in SC vs. 0.0 [IQR 0.0–4.6] % in NC, P = 0.02), malapposed struts (48% in SC vs. 27% in NC, P = 0.006), and severe medial tear (59% in SC vs. 44% in NC, P = 0.03) as compared to NC. Importantly, ≥3 consecutive struts on surface calcified area (odds ratio [OR]: 6.5, P < 0.0001), strut malapposition (OR: 5.0, P < 0.0001), and lack of severe medial tear (OR: 2.5, P = 0.0005) were independent predictors of delayed strut coverage, which has been reported to be one of the major causes of stent thrombosis . In spite of the fact that 20% of the patients receiving PCI have severely calcified lesions on coronary angiography , however, limited in vivo data are available regarding vascular response following DES implantation in such lesions as assessed by serial optical coherence tomography (OCT) assessment.