BACKGROUND Genetic polymorphisms of drug efflux transporters as ATP-binding cassette subfamily B, member 1 (ABCB1) have been suggested to modulate antiepileptic drugs (AEDs) response. We aimed to explore the association of ABCB1 polymorphisms and AEDs resistance among epileptic patients. METHODS A total of 86 Jordanian epileptic patients treated with AEDs was included in the study. DNA was extracted from blood samples and genotyping and haplotypes analyses were conducted for Nine single nucleotide polymorphisms (SNPs) on the ABCB1 gene. RESULTS Data revealed that none of the examined SNPs were associated with resistance to AEDs neither on the level of alleles nor genotypes. However, strong association was found between rs2235048 (OR = 10.6; 95%CI = [1.89-59.8], p= 0.01), rs1045642 (OR = 14; 95%CI = [1.3-156.7], p= 0.02), rs2032582 (OR = 9.1; 95%CI = [1.4-57.3], p= 0.04) and rs1128503 (OR = 18.7; 95%CI = [1.6-222.9], p= 0.02), ABCB1 polymorphisms and resistance to AEDs among females but not males. Haplotype analysis revealed statistically significant associations. The strongest significant associations were for haplotypes containing 2677G_1236 T in two-SNPshaplotypes (OR = 4.2; 95%CI = [1.2-14.9], p = 0.024); three-SNPs-haplotypes (OR = 4.2; 95% CI = [1.2-14.9], p = 0.02); four-SNPs-haplotypes (OR = 4.1; 95%CI = [1.2-14.3], p = 0.026). CONCLUSIONS Data suggests that there is a gender dependent association between ABCB1 genetic polymorphisms and response to AEDs. Additionally, ABCB1 haplotypes influence the response to AEDs. Further investigation is needed to confirm the results of this study.