OBJECTIVE Quantitative analysis of epileptiform discharges (EDs) before and after the initiation of an antiepileptic treatment is a useful tool to objectively documentate the efficacy of an antiepileptic drug (AED). Aim of this study was to evaluate the effect of levetiracetam (LEV) on EDs, monitored with ambulatory EEG (A/EEG), in a limited series of patients with generalized epilepsy. METHODS We performed 24h A/EEG recording in basal condition and at follow-up after LEV therapy in 21 adult epileptic patients. Eleven received LEV as monotherapy and 10 as add-on. For each patient we quantified total epileptic activity considering the following parameters: total number, total duration, maximal duration and median duration of EDs. Self-reported information on the effect of LEV on clinical seizures was also collected, to determine the electro-clinical correlation. RESULTS A high variability of the response to LEV was observed in the monotherapy group, without statistical differences for all the parameters investigated. A significant reduction of the total number of seizures (113.6 vs. 41.2; p=.01) was observed in patients in add-on therapy. The modifications of epileptiform EEG abnormalities did not necessarily correlate with the self-reported clinical impressions. CONCLUSIONS The quantification of EDs monitored by A/EEG provides a useful objective support for evaluating the neurophysiologic profile and the real efficacy of an antiepileptic treatment. In our patients LEV was able to significantly reduce the EDs only in add-on therapy. Further larger studies are necessary to clarify the effects of LEV on electro-clinical features of generalized epilepsy.