Although environmental factors are important, there is considerable evidence that genes also have a significant role in the pathogenesis of obesity. We conducted a population-based study to investigate the relationship between candidate genes for obesity (UCP1, UCP2, ADRA2B, ADRB3, LEPR, VDR and ESR1) and adiposity measures (body mass index, body fat percentage, weight, waist circumference and waist-hip ratio) in terms of individual gene and gene x gene interaction in models unadjusted and adjusted for covariates (age, years since menopause, educational level and total energy intake). Postmenopausal women with TC genotype of ESR1 gene had higher body fat percentage than those with TT genotype in the models unadjusted and adjusted for the covariates (P = 0.006 in adjusted model). In multiple logistic regression analysis, BsmI and ApaI SNPs of VDR genes were significantly associated with overweight and obesity. The UCP2-VDR ApaI interaction to susceptibility of overweight and obesity was first observed from logistic regression analysis, and then confirmed in the multifactor dimensionality reduction method unadjusted and adjusted for the covariates. This interaction had 69.09% prediction accuracy for overweight and obesity (P = 0.001, sign test). In conclusion, the study suggests the significant association of ESR1 and VDR genes with adiposity measures and the UCP2-VDR ApaI interaction to susceptibility to being overweight and obesity in postmenopausal Vietnamese women.