The cystathionine β-synthase (CBS) 844ins68 polymorphism, methionine synthase (MS) A2756G SNP, and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T SNP are associated with homocysteine (Hcy) level in humans. Elevated Hcy level is considered a risk factor for atherosclerotic diseases among Asian populations. Therefore, the three polymorphisms may vary the risk for developing such diseases in Singaporeans. In this study, the three polymorphisms were determined in a group of unrelated healthy Singaporeans (273 Chinese, 127 Indians, and 156 Malays). Regarding allele frequencies, Indians had the highest frequencies of the CBS insertion allele (2.0%) and the MS 2756G allele (26.4%), while Chinese had the highest MTHFR 677T allele frequency (27.5%). In addition, the MTHFR 677T allele was found significantly lower in Chinese males than in their female counterparts. As the CBS insertion allele was suggested to be associated with lower Hcy level, whereas the MS 2756G allele and the MTHFR T/T genotype were related to higher Hcy level, the MS A/G or G/G genotype and the MTHFR T/T genotype were considered double genetic risk factors for elevated Hcy level. The frequency of such double genetic risk was 0.7% (4 subjects) in the total population consisting of 3 Chinese (1.1%) and 1 Malays (0.6%). No MTHFR T/T genotype was found in Indians. Such results suggested that Chinese could have higher Hcy levels than Malays while the situation for Indians was complicated. Since human Hcy levels are also affected by environmental factors, further studies are required to better evaluate the association between these three polymorphisms and Hcy levels and/or disease susceptibilities in Singaporeans.