Epilepsy surgery is associated with a risk of cognitive deterioration, but improvement has also been reported. Improvements have mostly been attributed to seizure control, neglecting changes in drug treatment during the observation period. We evaluated whether changes of antiepileptic treatment affect cognitive outcome one year after epilepsy surgery.This retrospective study evaluated the impact of quantitative and qualitative antiepileptic drug changes on postoperative outcome on cognition (executive functions, episodic memory) and mood in 116 epilepsy surgery patients, controlling the results for seizure outcome (seizure free yes/no) and site of surgery (87 temporal lobe, 29 extratemporal lobe resections).At baseline, 60% of all patients showed impairment in executive functions, 54% in memory, 49% in mood. Postoperatively, 65% of the patients were seizure free. Executive functions, memory, and mood improved in 22%, 10%, and 32%, respectively, and deteriorated in 15%, 21%, and 11%. Drugs were changed quantitatively (change of drug load) and qualitatively (optimization in regard to side effect profiles). According to MANCOVA and individual level analyses, executive functions changed significantly with altered drug load. This was confirmed by partial correlations when controlling for seizure outcome. Memory outcome was more strongly determined by site of surgery. Mood improved non-specifically. However, qualitative drug change had some positive effect on postoperative memory and mood.The data highlight the relevance of AED changes for cognitive outcome after epilepsy surgery. Drug load reduction and selection of drugs with favorable side effect profiles significantly release cognitive functions thereby supporting recovery after epilepsy surgery.