Objective To investigate the relationship between Trp64Arg mutation in the β3-adrenergic receptor (β3-AR) gene and the incidence of hypertension in obese subjects. Methods A seven-year follow-up study was conducted in 377 simple obese subjects who had Trp64Arg mutation in the β3-AR gene and some clinical metabolic parameters, such as body mass index, waist circumference, waist-hip ratio, blood pressure, lipid profile, fasting blood glucose, fasting insulin and insulin resistance index (HOMA-IR) were measured in the year of 2000 and 2007. Results The results of follow-up indicated that the incidence of hypertension in Trp64Arg heterozygote subjects were higher than that in Trp64Trp homozygote subjects (52.7% ,69/131 vs 37.0% ,91/246,P < 0.01), the difference was only seen in male (59.5%, 50/84 vs 45.1%, 64/142, P < 0.05). The incidence of hypertension in both Trp64Trp homozygote and Trp64Arg heterozygote subjects were higher in obese male than those in obese female (P < 0.01 or <0.05). After seven years, the blood pressure increased (9.7 ± 4.3)/(5.4 ± 4.0) mm Hg(1 mm Hg = 0.133 kPa) in Trp64Trp homozygote,and (12.8 ± 5.2)/ (7.9 ± 4.7) mm Hg in Trp64Trp heterozygote subjects. Compared with that in Trp64Trp homozygote subjects, lipid profile, fasting insulin and HOMA-IR was increased significantly in Trp64Trp heterezygote subjects (P < 0.05). Logistic analysis showed that β3-AR gene mutation, male, central obesity and insulin resistance were associated with the incidence of hypertension in obese subjects. Conclusion The β3-AR gene Trp64Arg mutation is the independent risk factor in the incidence of hypertension in male.