INTRODUCTION Flow-diverters have revolutionized the endovascular treatment of intracranial aneurysms, offering a durable solution to aneurysms with high recurrence rates after conventional stent-assisted coiling. Events that occur after treatment with flow-diversion, such as in-stent stenosis (ISS) are not well understood and require further assessment. METHODS Six Pipeline Flex embolization devices (PED-Flex), six PED with Shield technology (PED-Shield), and four Solitaire AB devices were implanted in the carotid arteries (two stents per vessel) of four pigs. Intravascular optical coherence tomography (OCT) and digital subtraction angiography (DSA) images obtained on day 21 were compared to histological specimens. RESULTS A case of ISS in a PED-Flex device was assessed with OCT imaging. Neointima with asymmetrical topography completely covering the PED struts was observed. Histological preparations of the stenotic area demonstrated thrombus on the surface of device struts, covered by neointima. CONCLUSION This study provides evidence that endothelized thrombus is an underlying mechanism for ISS in flow-diverters. We postulate that similar cases of ISS are related to thrombus presence underneath endothelization, providing an explanation for stenosis occurrence and its reversibility.