BACKGROUND: Recent clinical studies are testing strategies for short (1-3 months) dual antiplatelet therapy following newer-generation drug-eluting stent (DES) placement. However, detailed biological responses to newer-generation DES remain unknown in humans. AIMS: We sought to evaluate early pathologic responses to abluminal biodegradable polymer-coated (BP-) DES compared with circumferential durable polymer-coated (DP-) DES in human autopsy cases. METHODS: The study included 38 coronary lesions with newer-generation DES implanted for <90 days (DP-DES=24, BP-DES=14) in 26 autopsy cases. The degree of strut coverage was defined as follows: grade 0 (bare), grade 1 (with fibrin or tissues/cells without endothelium), grade 2 (with single-layered endothelium), and grade 3 (with endothelium and underlying smooth muscle cell layers). RESULTS:  The duration following implantation was similar in DP- and BP-DES (median=20 vs 17 days). A total of 2,022 struts (DP-DES=1,297, BP-DES=725) were pathologically analysed. Focal grade 2 coverage was observed as early as 5 days after the implantation in both stents. The multilevel mixed-effects ordered logistic regression model demonstrated that BP-DES exhibited greater strut coverage compared with DP-DES (odds ratio [OR]: 3.64, 95% confidence interval [CI]: 1.37-9.67; p=0.009), which remained significant after adjustment for the duration following implantation and underlying tissue characteristics (OR: 2.74, 95% CI: 1.10-6.80; p=0.030). The predictive probability of grade 2 and 3 coverage was comparably limited at 30 days (DP-DES=17.1%, BP-DES=28.7%) and increased at 90 days (DP-DES=76.5%, BP-DES=86.6%). Both stents showed low inflammation and a similar degree of fibrin deposition. CONCLUSIONS: Single-layered endothelial coverage begins in the days after newer-generation DES placement, and BP-DES potentially exhibit faster strut coverage with smooth muscle cell infiltration than DP-DES in humans. Nevertheless, vessel healing remains suboptimal in both stents at 30 days.