We investigated the clinical features and surgical outcome of 17 patients with refractory epilepsy secondary to CNS infection who were referred to a tertiary center for presurgical evaluation. Six patients had a history of meningitis and 11 patients had a history of encephalitis. Median age at infection was three years (40 days-40 years). Time to seizure onset was shorter in the encephalitis group (median of 0.9 years versus 5.9 years in the meningitis group). MRI showed unilateral mesial temporal sclerosis (MTS) in all but one patient with meningitis (5/6). MRI in the encephalitis group showed unilateral MTS (four patients), bilateral MTS (three), porencephalic cysts (one) or no significant findings (three). Seizure semiology, following analysis of 127 seizures, included automotor seizures, complex motor/hypermotor seizures, dialeptic seizures and bilateral asymmetric tonic seizures. Neuropsychological assessment in patients with MTS frequently showed bilateral memory impairment (7 out of 12 MTS-patients), even in 4 patients with unilateral MTS, precluding epilepsy surgery. Six patients (two meningitis and four encephalitis patients) underwent a temporal lobe resection. All patients are either seizure-free (Class 1a) or are having only auras after surgery. One patient from the meningitis group underwent functional hemispherectomy and he is also seizure-free. In our series, MTS was the most common finding in refractory epilepsy after CNS infections. Bilateral memory deficits were often encountered in patients with MTS, even when unilateral, these deficits being a limiting factor for surgery. Good surgical outcome can be expected in selected patients with unilateral MTS and congruent memory deficits.