ObjectiveTo investigate the efficacy of vagus nerve stimulation (VNS) in patients with refractory magnetic resonance imaging (MRI)-negative epilepsy and to evaluate potential clinical predictors. MethodsA retrospective collection of efficacy data was conducted on 24 patients with intractable MRI-negative epilepsy treated with VNS, who were followed up for more than six months, at Beijing Tiantan Hospital and Beijing Fengtai Hospital from January 2016 to September 2023. Patients were divided into two subgroups based on their response to VNS: responders (≥50% reduction in seizure frequency) and non-responders (<50% reduction in seizure frequency). The relationship between preoperative clinical data and VNS efficacy was further analyzed to identify potential predictors of VNS efficacy. ResultsA total of 24 patients were included, with an average age of (14.26±8.39) years old. Seizure frequency was reduced by more than 50% in 37.5% of patients, and 8.3% of patients achieved seizure-free after VNS treatment. Preoperative seizure frequency and interictal epileptiform discharge type were significantly associated with VNS efficacy (P<0.05). Multivariate regression analysis showed that a monthly seizure frequency of less than 100 and focal interictal epileptiform discharges were independent predictors of VNS efficacy (P<0.05). ConclusionVNS is an effective treatment for patients with refractory MRI-negative epilepsy. Lower monthly seizure frequency and focal interictal epileptiform discharges are potential predictors of VNS efficacy. These findings provide important references for clinicians in selecting and evaluating patients for VNS treatment.