We hypothesized that human perivascular and subcutaneous adipose tissues hold distinct phenotypic signatures. We also evaluated the impact of clinical parameters on the adipose phenotype. Our overall goal is to understand the determinants of adipose biology so that this tissue can be manipulated therapeutically to lessen peripheral vascular disease.Perivascular and subcutaneous adipose tissues were collected from patients undergoing lower-extremity amputation (n = 27) and protein assayed for proinflammatory mediators (ie, interleukin 6, interleukin 8, leptin, tumor necrosis factor α, monocyte chemoattractant protein-1, and resistin), atheroprotective adiponectin, and the fibrinolysis inhibitor plasminogen activator inhibitor-1.Leptin (2.7-fold, P = .015), TNF-α (2.2-fold, P = .013), MCP-1 (1.5-fold, P = .047), and adiponectin (1.8-fold, P = .004) were more abundant in subcutaneous vs perivascular adipose tissue. Age positively correlated with perivascular adipose tissue PAI-1 expression (β = .64, P = .042), and hyperlipidemia negatively correlated with perivascular adiponectin (β = -1.18, P = .039).Human perivascular and subcutaneous adipose tissues hold distinct phenotypic signatures. In amputation patients, the subcutaneous adipose tissue proinflammatory phenotype was relatively attenuated in perivascular adipose tissue.