Background: The objective was to study the prevalence of human leukocyte antigen (HLA)-A*3101 allele among epileptic patients and to assess the safety and efficacy of antiepileptic therapy. Methods: 295 subjects were selected and divided into two groups, Group I had 192 epileptic patients and Group II had 103 normal healthy controls. After written informed consent, 30 ml of mouthwash sample was collected from each subject and DNA was extracted by standard salting-out technique and used for HLA-A*3101 genotyping by two-step nested allele-specific polymerase chain reaction amplification and agarose gel electrophoresis. Results: In Group I, 12 (6.25%) of the 192 patients were tested positive for HLA-A*3101 allele and all were taking carbamazepine (CBZ). Among them, 56 (30%) subjects had developed less severe adverse effects such as headache and giddiness, skin rashes and memory disturbances, and HLA-A*3101 was present in 8 of them while 136 had no adverse effects in which 4 of them were tested positive for the allele. In Group II, 3 (2.9%) of the 103 healthy controls were tested positive for the allele. No difference was found in response to antiepileptic therapy between allele positive and negative patients. Conclusion: The present study had shown that HLA-A*3101 is prevalent in 6.25% of the Indian epileptic population under study. The presence of this allele has a significant association with the development of mild cutaneous reactions like skin rashes. However, no difference was observed in allele positive patients in response to antiepileptic therapy in comparison with allele negative patients.