BACKGROUND: Seizures are common in children, but the causes and recurrence risk for children with a nonfebrile first seizure remain poorly understood. OBJECTIVE: In a prospective longitudinal study of children who presented with a first-time seizure, we investigated the viral etiology of associated infectious illnesses and sought to determine the risk of recurrent seizures stratified by fever and type of illness. PATIENTS AND METHODS: Children (aged 6 months to 6 years) were enrolled at the time of evaluation for their first seizure and followed monthly for up to 5 years. Seizure and illness data were collected through parent interviews and medical-record reviews. Stool, serum, and cerebrospinal fluid collected within 48 hours of the first seizure were evaluated for viral gastrointestinal pathogens. RESULTS: Of the 117 children enrolled, 78 (67%) had febrile seizures, 34 (29%) had nonfebrile-illness seizures, and 5 (4%) had unprovoked seizures. Children with nonfebrile-illness seizures were more likely than those with febrile seizures to have acute gastroenteritis (47% and 28%, respectively; P = .05). No significant differences in seizure recurrence were found between children with or without a fever at first seizure. Children with acute gastroenteritis at first seizure, regardless of fever, had a lower risk of seizure recurrence compared with children with other acute illnesses (hazard ratio: 0.28; 95% confidence interval: 0.09-0.80). CONCLUSIONS: Our results confirm the role of gastrointestinal illness as a distinguishing feature in childhood seizures. Children with this distinct presentation have a low rate of seizure recurrence and few neurologic complications.