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AIM: To assess the long-term efficacy of vagus nerve stimulation (VNS) in Dravet syndrome and identify key factors influencing treatment response.METHOD: We conducted a two-center, retrospective cohort study of 15 patients (six females, nine males; median age at seizure onset 4 months [range 2-12 months]) with Dravet syndrome who underwent VNS implantation. Seizure frequency was evaluated over 12 months and up to 10 years after implantation. Linear mixed-effects regression was used to analyze the impact of antiseizure medications (ASMs) and VNS parameters on seizure outcomes.RESULTS: A 50% or greater reduction in seizure frequency was observed in 93.3% (14 of 15) of patients at 12 months and 86.7% (13 of 15) of patients across the 10-year follow-up. This seizure reduction was independent of ASM use; the VNS duty cycle was a significant predictor of seizure reduction. Two individuals (13.3%) experienced minor adverse events.INTERPRETATION: VNS provides durable seizure reduction in Dravet syndrome, independent of ASM adjustments. These findings highlight the importance of early VNS initiation and parameter optimization in managing genetically defined epilepsy syndromes.