There is controversy about the relationship between ACE I/D polymorphism and health. Seventy-four healthy adults (n = 28 women; 22.5 ± 4.2 years) participated in this cross-sectional study aimed at determining the influence of ACE I/D polymorphism, ascertained by polymerase chain reaction, on cardiometabolic risk (i.e., waist circumference, body fat, blood pressure (BP), glucose, triglycerides, and inflammatory markers), maximal fat oxidation (MFO), cardiorespira-tory fitness (maximal oxygen uptake), physical activity and diet. Our results showed differences by ACE I/D polymorphism in systolic BP (DD: 116.4 ± 11.8 mmHg; ID: 116.7 ± 6.3 mmHg; II: 109.4 ± 12.3 mmHg, p = 0.035) and body fat (DD: 27.3 ± 10.8%; ID: 22.6 ± 9.7%; II: 19.3 ± 7.1%, p = 0.030). Interestingly, a genotype*sex interaction in relativized MFO by lean mass (p = 0.048) was found. The DD polymorphism had higher MFO values than ID/II polymorphisms in men (8.4 ± 3.0 vs. 6.5 ± 2.9 mg/kg/min), while the ID/II polymorphisms showed higher R-MFO values than DD polymorphism in women (6.6 ± 2.3 vs. 7.6 ± 2.6 mg/kg/min). In conclusion, ACE I/D polymor-phism is apparently associated with adiposity and BP, where a protective effect can be attributed to the II genotype, but not with cardiorespiratory fitness, diet and physical activity. Moreover, our study highlighted that there is a sexual dimorphism in the influence of ACE I/D gene polymorphism on MFO.