Vagus nerve stimulation (VNS) has been widely used as an effective treatment for patients with drug-resistant epilepsy (DRE). However, little is known about grey matter (GM) and white matter (WM) microstructure changes caused by VNS. This study aimed to detect consistent GM and WM alterations in epilepsy patients with vagus nerve stimulators.The diffusion tensor imaging data was acquired from 15 patients who underwent VNS implantation. The voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to detect group differences in GM and WM microstructure and explore their correlation with postoperative seizure reduction.After 3 months of stimulation, GM density reduced in right cerebellum, left superior temporal gyrus, right inferior temporal gyrus and left thalamus, and increased in left cerebellum, left inferior parietal lobule, left middle occipital gyrus and left gyrus rectus. No significant volume changes had been found in 14 subcortical nuclei. The fractional anisotropy (FA) values reduced in left superior longitudinal fasciculus and left corticospinal tract, and increased in bilateral cingulum and body of corpus callosum. The mean diffusivity (MD) values reduced in right retrolenticular part of internal capsule, right posterior corona radiata and right superior longitudinal fasciculus. The seizure reduction had positive correlation trends with the volume reduction in left nucleus accumbens and right amygdala, and MD reduction in right medial lemniscus and right posterior corona radiata.The results showed that VNS could cause changes of GM density, WM FA and MD values in epilepsy patients. The volume and MD reduction in some subcortical structures might participate in the seizure frequency reduction of VNS.Copyright © 2021 Elsevier B.V. All rights reserved.