The peroxisome proliferator-activated receptor gamma 2 (PPARγ2) genotypes are related to obesity and the metabolic syndrome (MetS). A low level of cardiorespiratory fitness is also a strong determining factor in the development of MetS. This cross-sectional study was performed to investigate the influence of the interaction between the PPARγ2 genotype and cardiorespiratory fitness on the risk of MetS. Healthy Japanese men (n = 211) and women (n = 505) participated in this study. All subjects were divided into 8 groups according to sex, fitness level (high and low fitness groups), and age (younger, age < 40 yr; middle-aged/older, age ≥ 40 yr). The PPARγ2 genotypes (Pro12Ala and C1431T) were analyzed by real-time PCR with Taq-Man probes. Two-way ANCOVA with adjustment for age as a covariate indicated that fitness and the CC genotype of C1431T in the PPARγ2 gene interacted to produce a significant effect on MetS risk in younger men and that the risk of MetS in the CC genotype group with low cardiorespiratory fitness was significantly higher than that in the corresponding CT+TT genotypes or in the high fitness groups. There was no significant interaction between fitness and genotype in determining MetS risk in middle-aged/older men or in women in any group. With regard to the Pro12Ala genotype of the PPARγ2 gene, there were no significant differences in fitness or genotype effects nor were there any interactions between measurement variables. We concluded that the CC genotype of C1431T in the PPARγ2 gene together with low cardiorespiratory fitness may increase the risk of MetS in younger men (age < 40 yr), even with adjustment for age.