Although seizures in brain tumor patients are common, the knowledge on optimal anti-seizure therapy in this patient group is limited. An observational study was carried out using a database of all patients from the neuro-oncology service during the period 2000-2005, with data on seizure characteristics, therapy with AEDs, the underlying brain tumor and its treatment. A total of 140 brain tumor patients were studied of whom 23.6% had a low-grade glioma, 53.6% a high-grade glioma, and 22.8% belonged to a mixed group existing of ependymoma, meningioma, and brain metastasis. Epilepsy as the presenting sign was more frequent in low-grade vs. high-grade gliomas (69.7 vs. 52%, P = 0.087), and a total of 75.8% of patients developed seizures with low-grade and of 80.0% with high-grade gliomas. Of all 99 patients with seizures, 80.1% received valproic acid (VPA) as first choice, and either levetiracetam (LEV), carbamazepine (CBZ) or lamotrigine (LMT) as the most frequent next choice. Patients treated with a combination of VPA and LEV showed the highest percentage of responders (81.5%), with a decline in seizure frequency of more than two categories in 55.6% and seizure freedom in 59%. No correlation was found between the use of VPA and survival. A combination of VPA and LEV seems effective, if seizure control cannot be achieved by VPA alone. This indicates that adding levetiracetam may be preferable over sequential trials of AED monotherapy in treatment-resistant seizures in patients with brain tumors.