Introduction: Globally, the incidence of obesity is rising rapidly, not only in industrialized nations but also in developing countries consistent with which higher vaspin serum concentrations and increased vaspin mRNA expression in human adipose tissue were found to be associated with obesity and insulin resistance in humans. The present study is the first investigation in an Iranian population to examine the possible association of vaspin rs2236242 gene polymorphisms with overweight and obesity in Iranian women. Materials and Methods: This case-control study was conducted on 91 overweight, 47 obese and 133 healthy control women. The Vaspin rs2236242 gene polymorphism was analyzed using the tetra-amplification refractory mutation system-PCR (T-ARMS-PCR) method. Results: T allele frequency was 0.66, 0.76, 0.8 and A allele frequency was 0.34, 0.24, 0.2 for the control group, and overweight and obese patients, respectively. In the dominant genetic model (comparison of AA+AT vs. TT), A allele showed protective effects on overweight (OR:0.49, 95%CI: 0.28-0.84, P: 0.009) and obesity (OR:0.39, 95%CI: 0.19-0.76, P:0.006). Moreover, TT genotype in vaspin rs2236242 polymorphism are associated with increased risk of overweight and obesity in women.  Conclusions: To conclude, study results demonstrate a significant association between vaspin rs2236242 gene polymorphism, and overweight and obesity in Iranian women.