Recent studies have shown independent and opposite associations of hip circumference (HC) and waist circumference (WC) with glucose intolerance, insulin resistance, and type 2 diabetes mellitus. However, no studies have simultaneously considered the independent contributions of both markers to metabolic proinflammatory and atherosclerotic risk factors. In this study, we examine the independent associations of WC and HC with metabolic syndrome and with proinflammatory and atherothrombotic features. Independent associations of thigh muscle and adipose tissue (AT) compartments with metabolic features were also studied. Abdominal and thigh muscle and AT distributions were assessed by computed tomography in 140 overweight and obese women (mean +/- SD: age, 38.3 +/- 0.5 years; body mass index, 30.4 +/- 0.3 kg/m(2)). Blood lipids and inflammatory and atherothrombotic markers were measured. For a given WC, a larger HC was inversely associated with fasting insulin (beta = -0.288, P = .008), hemoglobin A(1c) (beta = -0.246, P = .041), and plasminogen activator inhibitor-1 concentrations (beta = -0.241, P = .023). Contrarily, WC was related with an unfavorable metabolic profile. For a given WC, higher total thigh AT and total thigh subcutaneous AT masses were associated with lower hemoglobin A(1c) (beta = -0.244, P = .049; beta = -0.233, P = .049) and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (beta = -0.252, P = .040; beta = -0.245, P = .037). In addition, total thigh AT was related with leptin (beta = 0.310, P = .012), whereas total thigh subcutaneous AT revealed opposite associations with fasting insulin concentrations (beta = -0.239, P = .034). Total thigh muscular tissue mass was related with lower plasminogen activator inhibitor-1 (beta = -0.164, P = .049) and fibrinogen concentrations (beta = -0.222, P = .018). In conclusion, HC revealed independent and opposite associations with insulin resistance and atherothrombotic disturbances. Contrarily, a larger WC predicted an increased metabolic risk. These contrasting effects in diabetogenic and atherothrombotic disturbances were, respectively, mediated by gluteofemoral AT and thigh muscle tissue. Besides body mass index and WC screening relevance, HC can contribute to additionally predict health risk in overweight and obese women.