Several genes play a major role in obese phenotypes, and studies suggest that genetic variations among individuals, as well as their lifestyles, may bring about different body compositions. Among these genes, LEP, which codifies leptin, and the LEPR gene encoding its receptor were extensively studied for variants that could explain the obese phenotype. The LEPR p.Q223R gene polymorphism was analyzed in a sample of obese and nonobese individuals from Brazil to evaluate the role of this polymorphism in the obese phenotype in the population. Two hundred obese patients (60 males, 140 females, body mass index (BMI) >30 kg/m2) were screened, together with 150 lean or normal healthy individuals (63 males, 87 females, BMI <24 kg/m2). Genomic DNA was extracted and amplified by polymerase chain reaction (PCR). PCR products were digested with the restriction of endonuclease MspI, and separated by electrophoresis through an 8% polyacrilamide gel stained with silver nitrate. There was a significant difference in LEPR p.Q223R polymorphism frequency when comparing obese and lean subjects, with an odds ratio of 1.92 and a 95% confidence interval of 1.15–3.22 (P ¼ 0.013). There is a strong association of the LEPR p.Q223R gene polymorphism with obesity in Brazil.