Background: The therapeutic range of topiramate (TPM) blood level is not set because the efficacy and safety are not considered to be related to the level. However, the therapeutic target without side effects is necessary, so the optimal range of TPM blood level was analyzed in this study., Study Question: This study was conducted to evaluate the efficacy of TPM over 2 years and the utility of measuring blood levels of TPM during the follow-up of epileptic patients., Study Design: Thirty patients (18 males, 12 females; age range, 6 months-15 years) were treated with TPM for epilepsy. The initial dosage of TPM was 1-3 mg·kg·d. If the effect proved insufficient after 2 weeks, the dosage was increased to 4-9 mg·kg·d., Measures and Outcomes: Blood levels of TPM were measured by liquid chromatography-tandem mass spectrometry at 1, 6, 12, and 24 months after levels reached steady state. The efficacy of TPM was evaluated by the reduction in epileptic seizure rate (RR) at the time of blood sampling. Statistical analysis was performed using the Mann-Whitney U test., Results: A positive correlation was seen between blood levels and maintenance dosages, but no correlation was observed between blood levels and RR. Any significant difference was not identified in TPM levels between the effective group (RR ≥50%) and the ineffective group (RR <50%; P = 0.159). In the subgroup of patients who did not use valproic acid, a significant difference in TPM levels was apparent between the effective and ineffective groups (P = 0.029). The optimal range of TPM was advocated 3.5-5.0 μg/mL. The optimal range was set, so that ranges did not overlap between the effective and ineffective groups. No patients experienced any side effects., Conclusions: Measuring blood levels of TPM based on the classification of concomitant drugs and adjusting the dosage to reach the optimal range were recommended.