Vagus nerve stimulation (VNS) has emerged as a well-established therapeutic option for drug-resistant epilepsy (DRE). This study aims to assess treatment outcomes and prognostic factors in DRE patients undergoing VNS therapy.We conducted a single-center retrospective analysis of 44 consecutive DRE patients who underwent VNS implantation between 2017-2023. Primary efficacy endpoints were: 1) absolute seizure reduction (SR) percentage, and 2) responder rate (≥50% SR), evaluated during routine follow-up of seven years. Secondary outcomes included safety, assessed through adverse event monitoring and quality of life in epilepsy-31 (QOLIE-31), measured using standardized metrics. Multivariable logistic regression models were used to examined associations with three clinical predictors: gender, age at implantation, and preoperative epilepsy duration.The mean seizure reduction from baseline was 49.15%, with 21 patients (47.7%) meeting the responder criterion. Regression analysis identified a significant inverse relationship between epilepsy duration and treatment response (β = -0.1819, p = 0.0119 for age threshold 18; β = -0.1299, p = 0.0743 for age threshold 12). Device-related complications requiring surgical revision occurred in two cases (4.5%). Postoperative QOLIE-31 scores averaged 59.95 (±14.35) on standardized assessments.Our findings demonstrate the sustained efficacy of VNS in managing DRE, with nearly half of the patients achieving clinically meaningful seizure control. The observed inverse association between disease duration and treatment response highlights the potential benefits of earlier VNS intervention. Together with its favorable safety profile, these results support the role of VNS as an integral component of comprehensive epilepsy management.Copyright © 2025. Published by Elsevier Inc.