We aimed to find out if the serotonin receptor (HT102T>C) and serotonin transporter (STin 2) polymorphisms play any role in genetic susceptibility of migraine. For the study, 217 migraine patients and 217 healthy controls (HC) were recruited and genotyping was carried out using the Polymerase Chain Reaction and Restriction Fragment Length polymorphism (PCR-RFLP) method. All results were Bonferroni corrected. We could not find any significant differences in the genotype or allele frequencies in case of HT 102 T>C polymorphism between migraine patients and healthy controls (P value=0.224). No significant association was seen at allele and carrier levels. Sub-grouping the patients on the basis of gender or on basis of migraine type i.e. with or without aura also did not show any association. Similarly, no difference in genotype (P value=0.236), allele (P value=0.550) or carrier frequency (P value=0.771) in STin 2 VNTR polymorphism was observed between migraine patients. However, HT 102 TC genotype was observed to interact significantly with the STin 2.10/10 genotype in enhancing risk of migraine, both with and without aura. In conclusion, the HT102 T>C receptor and the STin 2 VNTR transporter polymorphisms, did not individually confer any significant risk of migraine or its clinical subtypes but the two polymorphisms appear to synergistically influence susceptibility to migraine. Serotonin transporter (STin2 VNTR) and receptor (HT 102T>C) polymorphisms; Migraine with aura (MA); Migraine without aura (MO); Genetic susceptibility