OBJECTIVE: We investigated whether vagus nerve stimulation (VNS) induces a positive shift of slow cortical potentials (SCPs) in patients with >50% seizure reduction (responders) but not in non-responders. METHODS: We analyzed routine clinical electroencephalograms (EEGs) from 24 patients who were undergoing seizure treatment by VNS. The patients were divided into 2 groups by hardware time constant (TC) of EEG: the TC 10-s group (10 patients) and TC 2-s group (14 patients). We compared SCPs at 5 electrodes (Cz and adjacent ones) between the 2 states of VNS: during stimulation and between stimulations. Seizure reduction was independently judged. Correlation between SCP (positivity or not) and seizure reduction (>50% or not) was estimated. RESULTS: In the TC 10-s group, the correlation between SCP and seizure reduction was significant (p<0.05) (i.e., both good results in 4 and both negative results in 5). In TC 2-s group, the correlation between SCP and seizure reduction was not significant (p=0.209). CONCLUSIONS: A positive shift of SCP recorded by using a TC of 10s could be a surrogate marker for VNS response. SIGNIFICANCE: SCP could be a biomarker of good responders to VNS.