Background Traumatic brain injury (TBI) has been recognized as an important and common cause of epilepsy since antiquity. Posttraumatic epilepsy (PTE) is usually associated with drug resistance and poor surgical outcomes, thereby increasing the burden of the illness on patients and their families. Vagus nerve stimulation (VNS) is an adjunctive treatment for medically refractory epilepsy. This study aimed to determine the efficacy of VNS for refractory PTE and to initially evaluate the potential predictors of efficacy. Methods We retrospectively collected the outcomes of VNS with at least a 1-year follow-up in all patients with refractory PTE. Subgroups were classified as responders and non-responders according to the efficacy of VNS (≥50% or <50% reduction in seizure frequency). Preoperative data were analyzed to screen for potential predictors of VNS efficacy. Results In total, forty-five patients with refractory PTE who underwent VNS therapy were enrolled. Responders were found in 64.4% of patients, and 15.6% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time, with 37.8, 44.4, 60, and 67.6% at the 3-, 6-, 12-, and 24-month follow-ups, respectively. After multivariate analysis, generalized interictal epileptic discharges (IEDs) were found to be a negative predictor (OR: 4.861, 95% CI: 1.145–20.632) of VNS efficacy. Conclusion The results indicated that VNS therapy was effective in refractory PTE patients and was well tolerated over a 1-year follow-up period. Patients with focal or multifocal IEDs were recognized to have better efficacy after VNS therapy.