In clinical practice, it is important to predict as soon as possible after diagnosis and starting treatment, which children are destined to develop medically intractable seizures and be at risk of increased mortality. In this study, we determined factors predictive of long-term seizure and mortality outcome in a population-based cohort of 102 children. At the end of the 40-year median follow-up, since their first seizure before the age of 16 years, 95 (93%) of 102 patients had entered one or more one-year remissions (1YR). In contrast, 7 (7%) patients never experienced any 1YR and their epilepsy was considered drug-resistant. Two factors present early in the course of treatment were found to be associated with adverse outcome. Having weekly seizures during the first year of treatment carried an 8-fold risk [hazard ratio 8.2 (1.6-43.0), P = 0.0125] of developing drug resistant epilepsy and a 2-fold risk of never entering terminal 1YR [hazard ratio 2.7 (1.5-5.0), P = 0.0010]. Having weekly seizures prior to treatment only slightly increased the risk to never enter terminal 1YR [hazard ratio 1.7 (1.04-2.9), P = 0.0350]. Thirteen of 102 patients (13%) died during follow-up. Long-term mortality was 9-fold higher for patients with symptomatic epilepsy [hazard ratio 9.0 (1.8-44.8), P = 0.0071]. Mortality was not, however, increased by having weekly seizures prior to or during the first year of treatment versus fewer seizures. Early seizure frequency can predict long-term seizure control during antiepileptic drug treatment, but not mortality. Aetiology, however, is predictive of both seizure outcome and mortality in childhood-onset epilepsy. Using these criteria allows early identification of children destined to develop intractable epilepsy and increased mortality.