Several characteristics of neointimal tissues, including neoatherosclerotic progression, have been reported in lesions with in-stent restenosis (ISR). However, the effects of these characteristics on outcomes after percutaneous coronary intervention (PCI) for ISR lesions remain unclear. We assessed the relationships between neointimal tissue characteristics and the occurrence of periprocedural myonecrosis (PMN) after PCI in ISR lesions. We investigated 72 ISR lesions in 72 patients with stable angina pectoris (SAP) who underwent pre- and post-revascularization optical coherence tomography (OCT) and coronary angioscopy (CAS). All lesions were classified as with PMN, defined by an elevated peak high-sensitivity cardiac troponin-T level during the 24-h post-PCI period, and without PMN. PMN was observed in 23 (31.9 %) lesions. PMN lesions had higher frequencies of OCT-derived thin-cap fibroatheroma (26.1 vs. 6.1 %, P = 0.03), CAS-derived intensive yellow neointima (30.4 vs. 10.2 %, P = 0.04), neointima with complex surface (60.9 vs. 28.6 %, P = 0.01), and CAS-derived atheromatous appearance (CAS-AAP), defined as yellow plaque including complex thrombi underneath disrupted neointimal coverage after ballooning (47.8 vs. 16.3 %, P = 0.008) at the most stenotic sites inside stents, compared to lesions without PMN. Multivariate logistic regression analysis identified CAS-AAP (odds ratio: 3.568, 95 % confidence interval: 1.109–11.475, P = 0.033) as an independent predictor of PMN. For ISR lesions in SAP patients, an OCT- and CAS-based assessment of neointimal tissue characteristics might help to predict the occurrence of PMN.