Background: The effect of Vagus nerve stimulation (VNS) therapy following major resective surgeries has been reported. However, the effect of VNS therapy following multiple-subpial-transections (MST) has not been reported. The objective of this paper is to examine the beneficial effect of VNS therapy following MST. Methods: There are 22 patients aged 10 -55 years. Male/female distribution is 11/11 and follow-up is 24 -148 months (median of 120 months). Seizure foci were bilateral in 9 patients, multi-lobar (unilateral) in 12 patients and single-lobar in 1 patient. MST was performed over broad areas in and around the seizure foci. VNS implantation was done when the response to MST procedure was poor (1 patients), or there was recurrence of seizures (21 patients). Interval between MST and VNS implanttation varied from one month to three years (median of 2 years). Results: Thirteen patients (59%) are seizure free (Engel' Class I), 8 (36.5%) have greater than 90% reduction in seizure frequency (Class II), and 1 (4.5%) has between 50% -90% reduction in seizure frequency (Class III). Conclusion: The results show that VNS therapy produced meaningful improvement in seizure outcome in all patients with extra-temporal seizures that had inadequate response to MST.