To explore abnormalities of topological properties in drug-resistant epilepsy (DRE) patients after vagus nerve stimulation (VNS) by analyzing brain functional networks using graph theory.Fifteen patients and eight healthy controls (HC) were scanned separately with resting-state functional magnetic resonance imaging (rs-fMRI). Graph theoretical analyses were chosen to compare the global (small-world parameters [γ, λ, σ, Cp, and Lp], and network efficiency [Eg and Eloc]), and nodal (BC, DC, and NE) properties in preoperative patients (EPpre), postoperative patients (EPpost) and HC.HC, EPpre and EPpost all satisfied the criteria for small-world properties (σ > 1) within the sparsity range of 0.05-0.5. Compared with EPpre, EPpost performed higher in λ and Eloc but lower in γ, σ, and Cp. Compared with HC, EPpre exhibited decreased BC, DC or NE in the right inferior frontal gyrus, right superior temporal gyrus, bilateral cingulate gyri, right supplementary motor area, right superior occipital gyrus, right Heschl gyrus, and left calcarine fissure; increased BC in the left postcentral/precentral gyrus, right paracentral lobule, left rolandic operculum, and left supramarginal gyrus, and increased NE in the right caudate nucleus. Compared with EPpre, EPpost showed increased BC, DC or NE in the bilateral inferior frontal gyrus, right middle frontal gyrus, bilateral cingulate gyri, right superior temporal gyrus, and right Heschl gyrus and decreased BC in the left fusiform gyrus.VNS downregulated small-world properties in DRE, and caused changes in some key nodes to reorganize the transmission ability of the large-scale network.Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.