OBJECTIVE: This study aimed to determine the associations of the Homeostatic Model of Assessment-insulin resistance (HOMA-ir), acanthosis nigricans, high-sensitivity C-reactive protein (hs-CRP), and plasminogen activator inhibitor-1 (PAI-1) with 2 of the commonly used definitions of metabolic syndrome (Adult Treatment Panel III [ATP III] and International Diabetes Federation [IDF]) among reproductive-age, healthy, free-living African American women. METHODS: A pilot study with a cross-sectional design examined 33 African American women aged 20 to 46 years (mean [SD], 31.24 [7.25] years) for the presence of metabolic syndrome determined by ATP III and IDF criteria, insulin resistance (HOMA-ir and/or acanthosis nigricans), degree of inflammation (hs-CRP), and presence of dysfibrinolysis (PAI-1). RESULTS: HOMA-ir identified insulin resistance in 27 (81.8%) women, whereas the presence of acanthosis nigricans indicated that 16 (48%) of these women manifested insulin resistance. Metabolic syndrome was found in 7 women (21.2%) by ATP III or in 9 (27.3%) women by IDF criteria. Bivariate correlations showed associations between HOMA-ir and waist circumference, body mass index (BMI), acanthosis nigricans, and the ATP III and IDF definitions for metabolic syndrome. Plasminogen activator inhibitor-1 was significantly correlated with waist circumference, BMI, fasting glucose, HOMA-ir, and ATP III. Both HOMA-ir and PAI-1 were significantly and negatively correlated with high-density lipoprotein cholesterol. High-sensitivity CRP was significantly correlated with BMI and 2-hour postglucose. CONCLUSION: Both dysfibrinolysis (PAI-1 levels) and insulin resistance (HOMA-ir), when individually regressed on the ATP III definition of metabolic syndrome, explained 32% and 29% of the respective variance. The addition of HOMA-ir measurement may significantly improve early recognition of cardiometabolic risk among reproductive-age African American women who have not yet met the criteria for the ATP III or IDF definitions of metabolic syndrome. Likewise, acanthosis nigricans is potentially a clinically significant screening tool when used to determine early recognition of insulin resistance and/or cardiometabolic risk among this population. African American women's risk for cardiovascular disease is likely underestimated based on the sole use of ATP III criteria for diagnosis of metabolic syndrome. Clinicians should consider a broader definition of risk than that contained within ATP III. Inclusion of biomarkers of inflammation and dysfibrinolysis, along with measures of insulin resistance, may add to early detection of cardiometabolic risk and ultimate reduction in cardiovascular health disparities among African American women. © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.