PURPOSE: To characterize preprocedural coronary atherosclerotic lesions derived from CCTA and assess their association with in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). MATERIALS AND METHODS: This retrospective cohort-study included patients who underwent CCTA for suspected coronary artery disease, subsequent index angiography including PCI and surveillance angiography within 6-8 months after the index procedure. We performed a plaque analysis of culprit lesions on CCTA using a dedicated plaque analysis software including assessment of the surrounding pericoronary fat attenuation index (FAI) and compared findings between lesions with and without ISR at surveillance angiography after stenting. RESULTS: Overall 278 coronary lesions in 209 patients were included. Of these lesions, 43 (15.5 %) had ISR at surveillance angiography after stenting while 235 (84.5 %) did not. Likewise, plaque composition such as volume of calcification [129.8 mm CONCLUSION: Coronary lesions associated with ISR at surveillance angiography demonstrated differences in the arrangement of calcified portions as well as an increased lesion-specific pericoronary fat attenuation index at baseline CCTA. This latter finding suggests that perivascular inflammation at baseline may play a major role in the development of in-stent restenosis.