Febrile seizure is the most common neurologic disorder in infants and children. This study aimed to elaborate safe and effective therapy for preventing FS recurrence by levetiracetam (LEV). A prospective study was performed in two groups of children, the no treatment group (n=51, 24.1±9.0 months) and the LEV treatment group (n=45, 23.3±8.9 months). The findings demonstrated that a significant difference (P<0.01) was observed between the no treatment group 51.0% (26/51) and LEV treatment group 15.5% (7/45) in terms of FS recurrence after 50 weeks. FS recurrence/fever episode was 12.4% (12/97) in the LEV treatment group and 51.8% (57/110) in the no treatment group. Furthermore, LEV administration significantly improved (P<0.001) epileptiform + nonspecific EEG abnormalities (17.8%; 8/45), as compared with the no treatment group (68.6%; 35/51). In conclusion, LEV could function as an effective therapeutic agent for the prevention of FS recurrence and reducing the frequency of fever episodes. Furthermore, LEV administration significantly improved nonspecific EEG abnormalities, which may be used as a clinical monitoring index for LEV treatment in patients with FS.