Two common single nucleotide polymorphisms (SNPs) within the COL1A1 gene and the C677T variant within the methylenetetrahydrofolate reductase (MTHFR) gene have been studied for correlation with bone mineral density (BMD) in 126 postmenopausal Maltese women (55.6 ± 7.1 years). All polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while BMD at the lumbar spine (LS), femoral neck (FN), Ward's triangle and trochanter was measured by dual energy X-ray absorptiometry (DEXA). The observed genotype frequencies were similar to those in other populations and were in Hardy-Weinberg equilibrium. No association was observed between polymorphisms in the COL1A1 gene and BMD, even after adjustment for age, body mass index (BMI) and years since menopause. The C allele of the C677T variant of the MTHFR gene had a negative effect on trochanter BMD when testing for genetic models of dominant and recessive alleles (independent sample t-test: p = 0.03). Genotype frequencies of both genes did not differ significantly between normal women and those with a low BMD at either the LS or FN.