OBJECTIVE: We examined the relationship among iron stores, the metabolic syndrome, and insulin resistance. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 6,044 adults >20 years of age who participated in the Third National Health and Nutrition Examination Survey. Metabolic syndrome was defined as the presence of at least three of the following: elevated blood pressure, low HDL cholesterol, elevated serum triglycerides, elevated plasma glucose, and abdominal obesity. Insulin resistance was estimated using homeostasis model assessment (for insulin resistance), fasting insulin, and triglyceride-to-HDL cholesterol ratio. RESULTS: After excluding individuals with likely hemochromatosis, mean serum ferritin values in premenopausal women, postmenopausal women, and men were 33.6, 93.4, and 139.9 microg/l, respectively. Metabolic syndrome was more common in those with the highest compared with the lowest levels of serum ferritin in premenopausal women (14.9 vs. 6.4%, P = 0.002), postmenopausal women (47.5 vs. 28.2%, P < 0.001), and men (27.3 vs. 13.8%, P < 0.001). Insulin resistance also increased across quartiles of serum ferritin for men and postmenopausal women and persisted after adjustment for age, race/ethnicity, C-reactive protein, smoking, alcohol intake, and BMI. CONCLUSIONS: Elevated iron stores were positively associated with the prevalence of the metabolic syndrome and with insulin resistance. Copyright 2004 American Diabetes Association