We have investigated the prevalence of the Factor II G20210A and Factor V G1691A single nucleotide polymorphisms (SNPs) in a South Indian-Tamil Nadu population. The SNP genotyping was performed using a polymerase chain reaction (PCR)/restriction fragment length polymorphism analysis and by a recently FDA-approved LightCycler real-time PCR assay. Of 72 samples that were genotyped, 4 (5.5%) patients were heterozygous for the Factor V SNP and no homozygous mutant patients were identified. None of the patients were shown to be either heterozygous or homozygous mutant for the Factor II SNP. All samples showed 100% concordance between the PCR/RFLP assay and the LightCycler assay. While this study identified the prevalence of the Factor V SNP to be similar to that of other reported populations, the absence of the Factor II allele is consistent with reports in more isolated populations. In addition, the results of this study do not support a role for these SNPs in acute myocardial infarction in the Tamilian population.