To identify early predictive factors of outcome in childhood epilepsy, the case records of all children with new-onset epilepsy presenting to a single neurology practice over a 10-year interval were reviewed. Only children with more than 2 years of follow-up were included. Cox regression analysis was used to identify factors predictive of remission (successful cessation of medication). One hundred ninety-six children (mean age 7.6 +/- 3.7 years at first seizure, mean follow-up 55 +/- 30 months) were identified. Ninety-eight of 196 children (50%) had an idiopathic epilepsy, 63 of 196 (32.1%) had cryptogenic epilepsy, and 35 of 196 (17.9%) had remote symptomatic epilepsy. At final assessment, 52.6% were in remission, 12.8% had a poor outcome (recurrent seizures on therapeutic antiepileptic drug levels within 6 months prior to the final assessment), and 6.9% were intractable (more than one seizure/month over 1 year with failure of three or more anticonvulsants). One year after initiating treatment, factors associated with a lower probability of remission included seizure recurrence in the 6- to 12-month interval after therapy initiation (hazard ratio 0.24), multiple seizure types (hazard ratio 0.40), and mental retardation at onset (hazard ratio 0.19). Factors predictive of a poor outcome included seizure recurrence in the 6- to 12-month interval after therapy initiation (odds ratio 21.6), more than one seizure type (odds ratio 8.9), and global developmental delay at onset (odds ratio 8.9). Factors predictive of intractability included multiple seizure types (hazard ratio 6.5), mental retardation at onset (hazard ratio 7.2), and seizure recurrence in the first 6 to 12 months of treatment (hazard ratio 70). It appears that response in the first 6 to 12 months on antiepileptic medication is predictive of outcome. Clinical features of the underlying epilepsy and concurrent neurologic conditions were independently associated with intractability and a lower probability of remission.