OBJECTIVE The purpose of this study was to provide the first national estimate on the prevalence of the metabolic syndrome and its components and the first ethnic-specific cutoff point for waist circumference in the Eastern Mediterranean Region. RESEARCH DESIGN AND METHODS This national survey was conducted in 2007 on 3,024 Iranians aged 25–64 years living in urban and rural areas of all 30 provinces in Iran. The metabolic syndrome was defined by different criteria, namely the definition of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), the International Diabetes Federation (IDF) criteria, and the modified definition of the NCEP/ATP III (ATP III/American Heart Association [AHA]/National Heart, Lung, and Blood Institute [NHLBI]). RESULTS The age-standardized prevalence of the metabolic syndrome was about 34.7% (95% CI 33.1–36.2) based on the ATP III criteria, 37.4% (35.9–39.0%) based on the IDF definition, and 41.6% (40.1–43.2%) based on the ATP III/AHA/NHLBI criteria. By all definitions, the prevalence of the metabolic syndrome was higher in women, in urban areas, and in the 55- to 64-year age-group compared with the prevalence in men, in rural areas, and in other age-groups, respectively. The metabolic syndrome was estimated to affect >11 million Iranians. The optimal cutoff point of waist circumference for predicting at least two other components of the metabolic syndrome as defined by the IDF was 89 cm for men and 91 cm for women. CONCLUSIONS The high prevalence of the metabolic syndrome with its considerable burden on the middle-aged population mandates the implementation of national policies for its prevention, notably by tackling obesity. The waist circumference cutoff points obtained can be used in the region.