Multiple drug resistance is a common problem in the treatment of epilepsy, and approximately 30% of patients continue to have seizures despite all therapeutic interventions. Among various classes of drug transporters, genetic variants of P-glycoprotein (P-gp) encoded by the ABCB1 (ATP-binding cassette subfamily B member 1) gene have been associated with drug-refractory epilepsy. Our aim was to investigate the effect of the 1236C>T(rs1128503), 2677G>T/A(rs2032582), and 3435C>T(rs1045642) single-nucleotide polymorphisms of ABCB1 (or MDR1) on drug resistance in north Indian patients with epilepsy. Genotyping was performed in 101 control subjects and 325 patients with epilepsy, of whom 94 were drug resistant and 231 drug responsive. Therapeutic drug monitoring for phenytoin, carbamazepine, phenobarbital, and valproate was also performed to confirm compliance in 20% of the patients. Genotype and haplotype frequencies of these polymorphisms did not differ between drug-resistant and drug-responsive patients. Our results demonstrate ABCB1 polymorphisms are not associated with drug resistance in north Indian epileptic patients.