BACKGROUND: We aimed to assess the associations between adiposity distribution and cardiometabolic risk factors among overweight and obese adults in China, and to demonstrate the sex differences in these associations. METHODS: A total of 1221 participants (455 males and 766 females) were included in this study. Percentage of body fat (PBF) of the whole body and regional areas, including arm, thigh, trunk, android, and gynoid, were measured by the dual-energy X-ray absorptiometry method. Central adiposity was measured by waist circumference. Clustered cardiometabolic risk was defined as the presence of two or more of the six cardiometabolic risk factors, namely, high triglyceride, low high density lipoprotein, elevated glucose, elevated blood pressure, elevated high sensitivity C-reactive protein, and low adiponectin. Linear regression models and multivariate logistic regression models were used to assess the associations between whole body or regional PBF and cardiometabolic risk factors. RESULTS: In females, except arm adiposity, other regional fat (thigh, trunk, android, gynoid) and whole-body PBF are significantly associated with clustered cardiometabolic risk, adjusting for age, smoking, alcohol drinking, physical activity, and whole-body PBF. One-SD increase in Z scores of the thigh and gynoid PBF were significantly associated with 80 and 78% lower odds of clustered cardiometabolic risk (OR: 0.20, 95%CI: 0.12-0.35 and OR: 0.22, 95%CI: 0.12-0.41). Trunk, android and whole-body PBF were significantly associated with higher odds of clustered risk with OR of 1.90 (95%CI:1.02-3.55), 2.91 (95%CI: 1.75-4.85), and 2.01 (95%CI: 1.47-2.76), respectively. While in males, one-SD increase in the thigh and gynoid PBF are associated with 94% (OR: 0.06, 95%CI: 0.02-0.23) and 83% lower odds (OR: 0.17, 95%CI: 0.05-0.57) of clustered cardiometabolic risk, respectively. Android and whole-body PBF were associated with higher odds of clustered cardiometabolic risk (OR: 3.39, 95%CI: 1.42-8.09 and OR: 2.45, 95%CI: 1.53-3.92), but the association for trunk PBF was not statistically significant (OR: 1.16, 95%CI: 0.42-3.19). CONCLUSIONS: Adiposity distribution plays an important role in the clustered cardiometabolic risk in participants with overweight and obese and sex differences were observed in these associations. In general, central obesity (measured by android PBF) could be the best anthropometric measurement for screening people at risk for CVD risk factors for both men and women. Upper body fat tends to be more detrimental to cardiometabolic health in women than in men, whereas lower body fat is relatively more protective in men than in women.