Background: Vagal nerve stimulation (VNS) is a palliative treatment option for drug-resistant epilepsy. The aim of this study was to describe the clinical and demographic features of selected patients scheduled for VNS and to evaluate the long-term efficacy of VNS in seizure control. Materials and Methods: Between 2006 and 2013, 32 consecutive epileptic patients (14 male and 18 female) were enrolled at our Institute for VNS implantation. In all cases resective surgery had previously been excluded by the use of a noninvasive presurgical study protocol. Mean age was 32 years (range 18–50), and mean epilepsy duration 23 years (range 11–39). All subjects were followed-up for at least 2 years (mean 6 years, range 2–9) after VNS implantation. Patients were considered responders when a reduction of seizures of more than 50 % was reported. Results: All patients had complex partial seizures, in 81 % of the patients with secondary generalization and in 56 % with drop attacks. Neurological examination revealed focal deficits in 19 % of the patients. Brain magnetic resonance imaging (MRI) was positive in 47 % of the patients. No surgical complications were observed in this series. Three patients were lost to follow-up. Twelve patients were classified as responders. Among the others, 1 patient experienced side effects (snoring and groaning during sleep) and the device was removed. Conclusions: Our data confirm that VNS is a safe procedure and a valid palliative treatment option for drug-resistant epileptic patients not suitable for resective surgery.