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Objective: To assess changes in the relative distribution of interictal epileptiform discharges (IEDs) and interictal EEG prognostic value in terms of surgical outcome between periods with full medication (FMP) and reduced medication (RMP) in patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS). Methods: Interictal scalp EEGs of 43 patients were evaluated for the presence of IEDs separately in a waking state (WS) and sleeping state (SS) during FMP and RMP. In each period, patients were categorized as having unitemporal or bitemporal IEDs. Surgical outcome was classified as Engel I or Engel II–IV; and alternatively as completely seizure-free (CSF) or not seizure-free (NSF). Results: There were significant changes in relative IED distribution between FMP and RMP during SS. The representation of patients with unitemporal IEDs declined from 37 (86%) in FMP during SS to 25 (58%) in RMP during SS (p=0.003). The relative IED distribution is a predictive factor for surgical outcome defined as Engel I or Engel II-IV in FMP during SS (p =0.020). The relative IED distribution could be a predictor for surgical outcome defined as CSF or NSF in both FMP during WS (p =0.043) and FMP during SS (p =0.015). When stepwise logistic analysis was applied, only FMP during SS was found to be an independent predictor for surgical outcome defined as Engel I or Engel II–IV (p =0.017), as CSF or NSF (p =0.018). Conclusion: The predictive value of relative IED distribution with respect to surgical outcome in interictal EEG is present only during FMP; the predictive value decreases with the reduction of AEDs caused by the change of relative IED distribution. [ABSTRACT FROM AUTHOR]