We assessed whether single nucleotide polymorphism rs1042615 of the vasopressin V1a receptor altered the indices of lifestyle-related diseases in middle-aged and older people (mean±SD: 64±7 years), and, if so, whether it also altered the effects of interval walking training (IWT). CC, CT, and TT carriers of rs1042615 (42, 118, and 64 men, respectively; 113, 263, and 154 women, respectively) performed IWT. We included 5 sets of 3-minute fast walking at ≥70% peak aerobic capacity for walking and 3-minute slow walking at 40% peak aerobic capacity per day for ≥4 days per week for 5 months. Before IWT, the body mass index and diastolic blood pressure (DBP) for men were 25.1±0.3 kg/m 2 (mean±SE) and 84±1 mm Hg in TT, higher than the 23.6±0.4 kg/m 2 and 78±1 mm Hg in CC, respectively ( P <0.01), differences that disappeared after IWT despite similar training achievement between groups ( P >0.6). After IWT, body mass index and DBP decreased in TT (−0.9±0.1 kg/m 2 and −5±1 mm Hg, respectively), more than in CC (−0.5±0.1 kg/m 2 and 1±1 mm Hg, respectively; P <0.05), with a greater decrease in low-density lipoprotein cholesterol in TT than CC carriers ( P <0.01). The decreases in DBP and low-density lipoprotein cholesterol were still greater in TT carriers even after adjustment for their pretraining values. On the other hand, for women, these parameters before IWT and their changes after IWT were similar among CC, CT, and TT carriers. Thus, polymorphism rs1042615 of the V1a receptor altered body mass index and DBP in middle-aged and older men and the training-induced responses of DBP and low-density lipoprotein cholesterol, whereas women did not show any of these responses.