Clinical conditions of long-term cure in childhood-onset epilepsy, defined as sustained remission off antiepileptic drug (AED) treatment, are not well known. To address that clinically important question, we determined clinical factors predictive of long-term seizure cure in a population-based cohort of 133 patients followed up since their first seizure before the age of 16 years. At the end of the 45-year follow-up (mean = 39.8, median = 44, range = 11-47), 81(61%) of the 133 patients had entered at least 5-year remission off AEDs, meeting our definition of cure. The 81 patients were seizure-free off AEDs for a mean of 34.4 (median = 38, range = 6-46) years and 59 (73%) of the 81 patients following the first standard medication until the end of follow-up (mean = 36.5, median = 39, range = 14-46 years). Four independent factors were found to be associated with cure compared with having seizures while on AEDs: seizure frequency less than weekly during the first 12 months of AED treatment (p = 0.002), pretreatment seizure frequency less than weekly (p = 0.002), higher IQ (>70; p = 0.021), and idiopathic or cryptogenic vs. symptomatic etiology (p = 0.042). Patients with seizure frequency of less than once a week during early treatment and idiopathic etiology had a ninefold chance to of being cured since the onset of the first adequate antiepileptic therapy until the end of follow-up compared with patients who a symptomatic etiology had at least weekly seizures while on AEDs (RR = 8.7,95% CI = 2.0-37.0; p < 0.001). In conclusion, IQ etiology, and seizure frequencies both in the first year of AED treatment and prior to medication appear to be clinical predictors of cure in childhood-onset epilepsy. (c) 2014 Elsevier Inc. All rights reserved.