A splice site variation (c. 603-91G > A or rs3812718) in the SCN1A gene has been claimed to influence efficacy and dose requirements of carbamazepine and phenytoin. We investigated the relationship between c. 603-91G > A polymorphism and response to antiepileptic drugs (AEDs) in 482 patients with drug-resistant and 401 patients with drug-responsive focal epilepsy. Most commonly used AEDs were carbamazepine and oxcarbazepine. The distribution of c. 603-91G > A genotypes was similar among drug-resistant and drug-responsive subjects, both in the entire population and in the groups treated with carbamazepine or oxcarbazepine. There was no association between the c. 603-91G > A genotype and dosages of carbamazepine or oxcarbazepine. These findings rule out a major role of the SCN1A polymorphism as a determinant of AED response.