© 2015 The Authors. Background: We hypothesized that higher concentrations of LDL particles (LDL-P) and leptin, and lower concentrations of HDL particles (HDL-P), and total and high molecular weight (HMW) adiponectin, would predict incident coronary heart disease (CHD) among severely obese postmenopausal women. Methods: In a case-cohort study nested in the Women's Health Initiative Observational Study, we sampled 677 of the 1852 white or black women with body mass index (BMI) ≥40kg/m2 and no prevalent cardiovascular disease (CVD), including all 124 cases of incident CHD over mean 5.0year follow-up. Biomarkers were assayed on stored blood samples. Results: In multivariable-adjusted weighted Cox models, higher baseline levels of total and small LDL-P, and lower levels of total and medium HDL-P, and smaller mean HDL-P size were significantly associated with incident CHD. In contrast, large HDL-P levels were inversely associated with CHD only for women without diabetes, and higher total and HMW adiponectin levels and lower leptin levels were associated with CHD only for women with diabetes. Higher total LDL-P and lower HDL-P were associated with CHD risk independently of confounders including CV risk factors and other lipoprotein measures, with adjusted HR (95% CIs) of 1.55 (1.28, 1.88) and 0.70 (0.57, 0.85), respectively, and similar results for medium HDL-P. Conclusions: Higher CHD risk among severely obese postmenopausal women is strongly associated with modifiable concentrations of LDL-P and HDL-P, independent of diabetes, smoking, hypertension, physical activity, BMI and waist circumference. General significance: Severely obese postmenopausal women should be considered high risk candidates for lipid lowering therapy.