Brain natriuretic peptide(BNP) and the N-terminal pro-brain natriuretic peptide (NTproBNP)are important cardiac biomarkers secreted by the heart in response to increased ventricular wall stress associated with heart failure. The aim of our case series was to prospectively evaluate the influence of vagus nerve stimulation (VNS) on the release of NTproBNP.Three children with medically refractory epilepsy and scheduled for implantation of the VNS device were included. Pre-implantation,NT-proBNP measurements were taken at two different occasions after seizure-free periods of at least three days. After implantation,NT-proBNP measurements were taken every 2 to 4 weeks, immediately before and immediately after up-regulation of the VNS. After VNS implantation, the pattern of NT-proBNP increase was consistent for all children. In a 12 year-old girl, NT-proBNP concentrations reached a maximum of an almost 10-fold increase. Thereafter, NTproBNP concentrations returned continuously to baseline. In a three year-old boy, NT-proBNP concentrations reached a maximum of an almost 7-fold increase, accompanied by manifestation of side effects(voice alterations, snoring).Thereafter, NT-proBNP concentrations decreased to almost 4-fold those at baseline. In an 8 year-old girl, NT-proBNP concentrations increased slightly without yet reaching a plateau. This case series suggests that NT-proBNP concentrations increase in response to VNS-induced autonomic influences involving endocrinological stress-response mechanisms typically associated with cardiac injury.Especially in patients with pre-existing cardiovascular dysfunction,measurement of NT-proBNP concentrations may help to identify patients with high baseline concentrations and possibly at greater risk for cardiac side effects.