BackgroundEpilepsy is a chronic disease affecting about 2% of the population and is considered a serious neurological disease. Despite its good prognosis, 20–30% of epileptic patients were not cured of their seizures even with the many trials of antiepileptic drug (AED) therapy. The resistance mechanism is still unclear, maybe due to the effect of the genetic factors on the bioavailability of the drugs. Consequently, the association between therapy resistance and the presence of a gene called “multidrug resistance 1 (MDR1)” had been proposed. Thus, the present study aimed to understand the relationship between the genetic polymorphism of MDR1C3435T and the resistance to AEDs.ResultA non-significant association was found between MDR1 C3435T single-nucleotide polymorphism (SNP) and drug-resistant epilepsy. However, there was statistical significance in the association between the drug type and the genotype distribution, in cases that were maintained on sodium valproate and MDR1C3435T genotype.ConclusionPossible involvement of the MDR1 gene C 3435T polymorphism with sodium valproate resistance clarifies the importance of genetic variability in response to the drug and may help to find novel genetic therapy for epilepsy, by targeting the biological mechanisms responsible for epilepsy in each specific individual. Future studies with bigger sample sizes and in other racial populations will be necessary.