Early postoperative seizures are defined as those that appear within the first week after surgery and are a well-known and feared complication in patients with supratentorial brain tumors. Few studies have investigated the value of pharmacological prophylaxis in the prevention of postoperative seizures in these patients and their outcome has not been consistent. Furthermore, the efficacy of the new generation of antiepileptic agents in the prophylaxis of perioperative seizures has not been assessed so far. We analyzed the data related to 150 patients harboring supratentorial brain gliomas with the aim to assess the efficacy of oxcarbazepine in preventing the occurrence or the recurrence of early postoperative seizures and its tolerability when it is rapidly titrated. Only four patients (2.7%) experienced seizures within the first week after surgery. Patients did not report disturbances during the titration phase. Regarding adverse events in the first week, six patients (4%) showed minor skin rash. Persistent symptomatic hyponatremia never occurred. Our data showed that oxcarbazepine can be a good alternative to traditional antiepileptic agents in the prevention of perioperative seizures being efficacy, ease of use (rapid titration in 3 days, not requiring close plasma concentration monitoring) and good tolerability (no major side effects during titration and during the first postoperative week) the key factors. Moreover, oxcarbazepine can be a valid choice when long-term therapy is required because of the low interaction with other drugs and the low hematological side effects.