Background/Objectives: To determine which component of the metabolic syndrome (MetS) is the best predictor of its development. Subjects/Methods: In this cohort study, 2279 subjects aged 20-87 years without MetS selected from among the participants of the cross-sectional phase of the Tehran Lipid and Glucose Study (TLGS) were followed up for development of MetS. Results: After a mean interval of 6.5 years, 462 and 602 new cases of MetS were diagnosed on the basis of the modified Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF) criteria, respectively. The adjusted odds ratio for development of MetS by ATP III criteria was highest for central obesity in men, 2.8 (2.2-3.7), and for triglycerides (TGs) in women, 2.8 (2.0-4.1). The adjusted odds ratio for the development of MetS by IDF criteria was highest for TGs in both men and women: odds ratio 2.8 (2.2-3.7) and 2.9 (1.9-4.3), respectively. A model that included waist circumference (WC) and TGs or WC and high-density lipoprotein (HDL) predicted MetS similar to a model that included all five MetS components. Conclusion: Screening for the timely prediction of the development of MetS should include measurement of WC, TGs and plasma HDL.