Vagus Nerve Stimulation (VNS) system is a fully implantable electrical stimulator, which stimulates the left vagus nerve to reduce or mitigate epileptic seizures among drug-resistant patients. Three years have passed since VNS was approved in Japan. Until now, more than 500 devices were implanted. However, changes in medical cost have not been reported yet in Japan. The aim of this study is to elucidate cost changes of VNS by comparing the direct medical cost between Pre-VNS treatment for 2 years and Post-VNS for 2 years. Seirei Hamamatsu General Hospital has experienced 87 VNS system implantations from July 2010 to November 2013. Among those, the medical costs of patients who had received the therapy for more than 2 years were surveyed in order to retrospectively compare 2-year antiepileptic drug costs pre- and post-VNS implantation. 17 patients with mean age of 28.6 years (range: 16-56) met the criterion of patients selection. Total direct medical cost in Pre-VNS for 2 years was 21,519,870 JPY and Post-VNS for 2 years was 11,597,610 JPY excluding drug cost. This change in cost was affected by reduced reimbursement codes mandated by the National Health Insurance System, including doctor's fee for diagnosis of epilepsy, EEG and image diagnosis. The 4 new antiepileptic drugs were approved after 2006 with extremely high prices, so that the cost changes occurring due to VNS implantation could not be comprehensively determined. This study may elucidate that VNS carries the changes in direct medical cost among the general epilepsy population. However, it does not mean the cost-effectiveness. Additionally the inclusion criterion for this study was that they had treatment and billing records for a period of 2 years before and after VNS implantation. Therefore the replacement cases were not included because period of the surveillance was too short. Longer term study will be required to understand the cost of VNS implantations including replacement.