Associations between the TAQIB and I405V polymorphisms and obesity risk were studied for a single locus as well as in combination. A total of 934 obese subjects and 924 normal controls were included in the study. TAQIB was associated with high-density lipoprotein (HDL) levels (P < 0.001), while I405V was associated with levels of low-density lipoprotein (P = 0.03) and total cholesterol (P = 0.007). Less common alleles of TAQIB and I405V were associated with decreased obesity risk and further drops in odds ratio (OR) were observed in carriers with rare homozygous alleles on both loci (OR = 0.659, P = 0.02). The TAQIB B2 allele was associated with reductions in both hip circumference (P = 0.034) and triceps skinfold thickness (TST) (P = 0.045), although this effect was completely abolished after controlling for HDL levels. The 405V variant was associated with reductions in hip circumference (P = 0.031), body fat composition (P = 0.039) and TST (P = 0.036); these effects were weakened (P < 0.1) after controlling for HDL levels. In conclusion, less common alleles of TAQIB and I405V appear to be modestly associated with obesity risk in an adult Chinese population. Adjustments for HDL levels completely (TAQIB) or partially (I405V) abolished the observed association.