Introduction: Febrile seizure (FS) is the most common causes of seizures in infants and toddlers. Although FS has a good prognosis, recurrence of seizures can occur in around 35% of affected children. Intermittent oral diazepam has been tried for prophylaxis in children with recurrent simple FS, but is associated with side effects. Melatonin has been used for treatment of insomnia, but the anticonvulsant effect of melatonin has also been reported. Objectives: To evaluate the efficacy of oral melatonin compared to oral diazepam for prevention of recurrent simple febrile seizures. Patients and Methods: This study was carried out on 60 children diagnosed with recurrent simple FS who attended Pediatric Neurology Clinic in Tanta University Hospital. Children were randomly allocated into two groups: the first group included 30 children who received oral melatonin 0.3mg/kg/8 hours. The other group included 30 children who received oral diazepam 1mg/kg/day divided into 3 doses. Both melatonin and diazepam were given only during the febrile illness. Patients were followed up monthly for 6 months for recurrence of febrile seizures and any side effects. Results: Both melatonin and diazepam have significantly reduced recurrence of febrile seizures (p<0.05), but there was no significant difference between patients treated with melatonin and patients treated with diazepam (p>0.05). Excessive sedation was the main side effect reported in children receiving oral diazepam. Conclusion: Oral melatonin was as effective as oral diazepam for prevention of recurrent simple FS. Melatonin was safe drug with no serious side effects on the studied children.