Extended-release oxcarbazepine (OXC) was introduced in Germany in January of 2008. In principle, this formulation should allow a better tolerability due to the less marked serum peak concentration of OXC prior to metabolization to its monohydroxy derivate (MHD) that is the active compound. Twenty-seven in-patients who had been referred to our epilepsy centre because of their difficult-to-treat localization-related epilepsies and had been on immediate-release OXC were abruptly switched to extended-release OXC at identical dosages. The adverse event profile (AEP) and the QOLIE-10 questionnaire were obtained immediately prior to and 5 days after this switch. On both days MHD fasting serum concentrations were also measured. After the switch a significant improvement of tolerability and quality of life was reported according to AEP and QOLIE-10 (p<0.001). Ameliorations were apparent in almost every patient (AEP: 26 of 27 patients, QOLIE-10: 23 of 27 patients). The improvement not explained by a drop of MHD levels. On the contrary and in line with preclinical data, serum levels of MHD rose significantly (p<0.001). We suggest that patients on extended-release OXC experience a lower serum concentration peak of the pro-drug OXC.