We studied the clinical characteristics, location of epileptogenic regions, and the surgical outcomes in 18 patients with intractable epilepsy associated with previous CNS infections. All patients underwent an extensive presurgical evaluation and 11 patients had intracranial EEG monitoring. On the basis of presurgical evaluation, epileptic regions were localized to the mesial temporal (n = 12) and the neocortical (n = 6) regions. The age of the time of CNS infection was significantly younger and the latent period of non-febrile seizures after CNS infection was longer in patients with mesial temporal lobe epilepsy (MTLE). MRI showed hippocampal atrophy and hippocampal signal changes in 11 of 12 patients with MTLE. Among 6 patients with neocortical epilepsy (NE) 5 patients had normal MRI and one showed cerebral hemi-atrophy. Surgery was successful (class I & II) in all patients with MTLE, however, in the patients with neocortical epilepsy, seizure-free results were not achieved in any patients after resective surgery (6 patients) and only 2 patients achieved Class II outcomes after a second epilepsy surgery consisting of neocortical resection. Patients with MTLE after CNS infection were differentiated from the group of neocortical epilepsy by an earlier onset of CNS infection, a prolonged latent period and a higher frequency of meningitis. The characteristic pathology in this group was hippocampal sclerosis and the surgical result was excellent. Neocortical epilepsy following CNS infection usually had no focal lesion on MRI and was associated with a relatively poor surgical result. This study suggested that the surgical outcome was influenced by the type of epileptic syndromes rather than the etiology of seizures. The association of MTLE with the younger age of CNS infections and with meningitis more frequently suggested that the neocortical neurons during infancy or early childhood may be more resistant to the epileptogenesis, or that the CNS infections in patients with MTLE might be milder in severity to cause selective injuries to the hippocampal neurons during their vulnerable stage.