There are limited data on the effect of dexmedetomidine on epileptiform electroencephalogram (EEG). The aim of this study was to investigate if dexmedetomidine will abolish epileptiform discharges in patients with medically refractory seizure disorders who were candidates for surgery to resect foci of epileptic activity. With approval from the Institutional Review Board and written informed consent, we enrolled 5 patients with medically intractable seizures who were undergoing continuous video/EEG monitoring. EEG and hemodynamic values were recorded from 15 minutes before, during, and for 60 minutes after a 60-minute dexmedetomidine infusion. Epileptiform discharges were counted for each 15-minute epoch during the study. Two of the 5 patients had a discrete spike focus in each hemisphere. Thus, we analyzed the activity of 7 distinct foci. Epileptiform activity did not decrease in any individual focus during dexmedetomidine infusion. Although dexmedetomidine did not have a statistically significant effect on interictal epileptiform activity for the group as a whole, the activity of 4 foci increased during dexmedetomidine infusion. Dexmedetomidine did not reduce seizure focus activity and thus may be a suitable anesthetic adjunct during seizure surgery.