Polymorphisms of the VKORC1 gene have been found to be associated with differences in response to warfarin dose. Little is known about VKORC1 variants in the heterogeneous populations of South East Asia. In Peninsular Malaysia, the majority of the population comprises three ethnic groups: Malays, Chinese and Indians. In our study, we determined the allele frequency of VKORC1 -1639>G in these three racial groups. Healthy blood donors and patients on warfarin were recruited and genotyped for VKORC1 (-1639G>A). A total of 452 subjects, including 233 patients receiving warfarin treatment, were recruited. A total of 206 Malays (46%), 147 Chinese (33 %) and 99 Indians (21%) were genotyped. The allele frequency of G is significantly higher in the Indian populations (86%) compared to Malays and Chinese (26.5% and 18.7% respectively), p<0.001. The homozygous GG genotype is only seen in 8% and 4% of the Malays and Chinese, respectively, compared to 78% of the Indians, p<0.0001. This finding suggests that Indians may have different genetic pool from the other 2 ethnic groups whilst Malays share similar genotypes to the Chinese.