The aim of this study was to investigate whether the Trp64Arg polymorphism of the β₃-adrenergic receptor gene ( ADRB3 ) is associated with weight changes in obese Japanese men at 4-year follow-up. The participants were 145 obese Japanese men [age: 35.8±5.3 y; body mass index (BMI): 27.5±3.3 kg/m²]. The participants were divided into two groups according to the Trp64Arg genotype: (1) with the Arg64 allele of the ADRB3 (Trp64Arg and Arg64Arg genotypes, n=50); (2) without the Arg64 allele of the ADRB3 (Trp64Trp genotype, n=95). The ADRB3 genotyping was performed by denaturing high performance liquid chromatography (DHPLC). Body weight, BMI, and blood pressure were determined at baseline and at 4 years. After 4 years, the participants with the Arg allele of the ADRB3 significantly increased their body weight (2.1±4.7 kg, p =0.002) and BMI (0.64±1.6 kg/m², p =0.006) whereas the participants without the Arg allele of the ADRB3 did not significantly change in these parameters (body weight: −0.36±4.2 kg, p =0.41; BMI: −0.24±1.5 kg/m², p =0.12). The results in this study showed that the Arg allele of the ADRB3 is associated with long-term changes in body weight in obese individuals. This polymorphism may become an indicator in personalized weight loss programs in obese men.