Objective To characterize the prevalence of metabolic syndrome (MetS), its five components and their pharmacological treatment in US adults by gender and race over time. Background MetS is a constellation of clinical risk factors for cardiovascular disease, stroke, kidney disease and type 2 diabetes mellitus. Methods Prevalence estimates were estimated in adults (≥20 years) from the National Health and Nutrition Examination Survey (NHANES) from 1999–2010 (in 2-year survey waves). The biological thresholds, defined by the 2009 Joint Scientific Statement, were: (1) waist circumference ≥ 102 cm (males), and ≥ 88 cm (females) (2) fasting plasma glucose ≥100 mg/dl (3) blood pressure of ≥130/85 mm Hg (4) triglycerides ≥150 mg/dl (5) high-density lipoprotein-cholesterol (HDL-C) <40 mg/dl (males) and <50 mg/dl (females). Prescription drug use was estimated for lipid-modifying agents, anti-hypertensives, and anti-hyperglycemic medications. Results From 1999/2000 to 2009/10, the age-adjusted prevalence of MetS (based on biologic thresholds) decreased from 25.5% (95%CI: 22.5–28.6) to 22.9% (20.3–25.5). During this period, hypertriglyceridemia prevalence decreased (33.5% to 24.3%), as did elevated blood pressure (32.3% to 24.0%). The prevalence of hyperglycemia increased (12.9% to 19.9%), as did elevated waist circumference (45.4% to 56.1%). These trends varied considerably by gender and race/ethnicity groups. Decreases in elevated blood pressure, suboptimal triglycerides and HDL-C prevalence have corresponded with increases in anti-hypertensive and lipid-modifying drugs, respectively. Conclusion The increasing prevalence of abdominal obesity, particularly among females, highlights the urgency of addressing abdominal obesity as a healthcare priority. The use of therapies for MetS components aligns with favorable trends in their prevalence.