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ObjectiveThis study was performed to clarify the utility of the Trail Making Test (TMT) in evaluating the effects of the course of epilepsy on cognitive function by evaluating the course of epileptic seizures and the results of the TMT over time.MethodsWe performed the TMT twice at a 1‐year interval for each patient with focal epilepsy. We performed multiple regression analyses with the first TMT scores as dependent variables and clinical features as independent variables. Next, we performed a multivariate analysis of covariance (MANCOVA) to evaluate the difference between the first and second TMT scores for patients in each seizure prognosis group.ResultsWe enrolled 132 adult patients in this study. Multiple regression analyses showed that longer active seizure periods were associated with worse first TMT‐B performance (β = .318, p < .001) and B–A (β = .377, p < .001) and that the number of antiseizure medicines was associated with worse first TMT‐A performance (β = .186, p = .025). In addition, topiramate and zonisamide adversely affected TMT performance. MANCOVA showed an interaction between the prognosis of TMT‐B performance and the seizure prognosis [F(2, 120) = 3.68, p = .028]. Subeffect tests revealed that the second TMT‐B performance improved only in the seizure improvement group [F(1, 10) = 10.07, p = .01].SignificanceEpileptic seizures were shown to be associated with both long‐term and dynamic adverse effects on cognitive function evaluated with the TMT in adult patients with focal epilepsy. Seizure control is important for improving the cognitive function of patients with epilepsy; however, the potential adverse effects of polypharmacy and some antiseizure medicines such as zonisamide and topiramate on cognitive function should be considered.