Monotherapy and combination therapy of valproic acid (VPA) may cause hyperammonemia. Several anti-epileptic drugs used in combination with VPA have reportedly been associated with the development of hyperammonemia. However, whether or not combination therapy with VPA and gabapentin (GBP) induces hyperammonemia remains unclear. We herein report a patient who developed hyperammonemia due to GBP in addition to VPA, phenytoin, phenobarbital, potassium bromide, clonazepam, lamotrigine, lacosamide and perampanel showing a need for awareness for hyperammonemia of the combination therapy.