AIMS Morphological assessment of neointimal tissue using optical coherence tomography (OCT) is important for clarifying the pathophysiology of in-stent restenosis (ISR) lesions. The aim of this study was to determine the impact of OCT findings on recurrence of ISR after paclitaxel-coated balloon (PCB) dilatation compared with plain old balloon angioplasty (POBA). METHODS AND RESULTS Between July 2008 and May 2012, we performed percutaneous coronary intervention for 214 ISR lesions using POBA + PCB (146 lesions, PCB group) or POBA only (68 lesions, POBA group). Morphological assessment of neointimal tissue using OCT, including assessment of restenotic tissue structure and restenotic tissue backscatter, was performed. We examined the association between lesion morphologies and mid-term (6-8 months) results including ISR and target lesion revascularization (TLR) rates. Both ISR and TLR rates of lesions with a homogeneous structure were significantly lower in the PCB group than those in the POBA group (ISR: 20.0 vs. 55.6%, P = 0.002, TLR: 12.7 vs. 37.0%, P = 0.019), but there was no difference between the two groups in ISR and TLR rates of lesions with a heterogeneous or layered structure. Both ISR and TLR rates of lesions with high backscatter were significantly lower in the PCB group than those in the POBA group (ISR: 19.8 vs. 52.5%, P < 0.001, TLR: 13.6 vs. 42.5%, P = 0.001), but there was no difference between the two groups in ISR and TLR rates of lesions with low backscatter. CONCLUSION Morphological assessment of ISR tissue using OCT might be useful for identifying ISR lesions favourable for PCB dilatation.