Despite the typically benign nature of febrile seizures, a large number of children with simple febrile seizures are overinvestigated and overtreated, according to the personal clinical experience of the treating doctors. The study objective was to analyze the effect of implementing an evidence-based medicine guideline on the management of febrile seizures in two European pediatric emergency departments. After introduction of a selected guideline, we analyzed the change in hospitalization rate and in the rate of execution of blood exams in children presenting with febrile seizures. Included in the study were 483 children. Clinical characteristics of seizures were similar both before and after implementation. Clinical management was modified after guideline introduction, because the hospitalization rate significantly decreased (respectively, from 57.3% to 20.5%, and from 16.9% to 3.2%), without any concomitant increase in readmission rate. Readmission cases were never due to severe bacterial infections. The proportion of patients who received blood examinations decreased significantly. We conclude that in both of the Emergency Departments studied, introduction of a guideline on febrile seizure positively modified clinical management. The availability of a guideline contributed to accelerating the process of improving welfare and positively influenced the quality of care.