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The aim of the present study was to evaluate the natural course of acute incomplete stent apposition (ISA) after second-generation everolimus-eluting stent (EES) when compared with first-generation sirolimus-eluting stent (SES) by using optical coherence tomography (OCT).From the OCT substudy of the RESET trial, we identified 77 patients (EES = 38 and SES = 39) who successfully underwent serial OCT examination at post-stenting and 8–12-month follow-up. The presence of ISA was assessed in the OCT images, and ISA distance was measured from the centre of the strut blooming to the adjacent lumen border. Incomplete stent apposition was observed in all EES and SES at post-stenting, and it was persistent in 26% of EES and 38% of SES at 8–12-month follow-up. Maximum ISA distance was significantly decreased during the follow-up period in both EES (315 ± 94–110 ± 165 μm, P < 0.001) and SES (308 ± 119–143 ± 195 μm, P < 0.001). Receiver-operating curve analysis identified that the best cut-off value of OCT-estimated ISA distance at post-stenting for predicting late-persistent ISA at 8–12-month follow-up in EES and SES was >355 and >285 μm, respectively.The second-generation EES showed better healing of acute ISA in comparison with the first-generation SES. Optical coherence tomography can predict late-persistent ISA after DES implantation and provide useful information to optimize PCI.