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Background/Aims After a study comparing drug-eluting stents (DESs) to sequential treatment with drug-eluting balloons (DEBs) and bare metal stents (BMSs), we retrospectively analysed strut malapposition and neointimal hyperplasia in de novo coronary lesions using optical coherence tomography (OCT) or intravascular ultrasonography (IVUS). Methods We obtained OCT data from 16 patients (eight per group) and IVUS data from 40 patients (20 per group). OCT or IVUS was performed after the index procedure and after 9 months. Parameters including obstruction volume due to neointimal hyperplasia (neointimal hyperplasia volume/stent volume, %), strut malapposition (% of malapposed struts), and intra-individual inhomogeneity of in-stent restenosis were compared. Results Although obstruction volume due to neointimal hyperplasia was significantly higher in the DEB-BMS group (14.90 ± 15.36 vs. DES 7.03 ± 11.39, p = 0.025), there was no difference in strut malapposition between the two groups (DEB-BMS 1.99 ± 5.37 vs. DES 0.88 ± 2.22, p = 0.856). The DEB-BMS group showed greater intra-individual inhomogeneity of in-stent restenosis pattern than the DES group. Conclusions Treatment with DEB followed by BMS failed to improve strut malapposition despite higher in-stent neointimal growth, probably because of the inhomogeneous inhibition of in-stent neointimal hyperplasia by DEB. DEB technology should be improved to obtain even drug delivery to the vessel wall and homogeneous prevention of neointimal growth comparable to contemporary DES.