Background/Objectives: This cohort study was conducted to evaluate the effect of waist change on metabolic syndrome (MetS) status and its parameters in 5720 participants, aged X20 years, of the Tehran Lipid and Glucose Study who were followed up for a mean of 6.6 years. Subjects/Methods: We measured waist circumference (WC) and MetS parameters at baseline (phase I: 1999) and at follow-up (phase III: 2008), and assessed this relationship across five groups: waist loss (oÀ2.0 cm); waist stable (À2.0 to 2.9 cm); mild (3.0-5.9 cm); moderate (6.0-8.9 cm) and large (X9.0 cm) waist gain. MetS was defined according to the International Diabetes Federation criteria. Results: In phase I, the mean (s.d.) waist gain was 88.8 cm (11.7). Between phases I and III, the mean (s.d.) waist gain was 5 cm (7.9). There was 16% (95% confidence interval (95% CI): 13.6-18.4) age-adjusted incident MetS and for every centimeter of WC gained over 6.6 years, the risk of MetS increased by 10% (odds ratio (OR) 1.10; 95% CI: 1.09-1.12). Compared with a stable WC in both genders, ORs for MetS for different waist gain groups were as follows: mild (OR 2.3, 95% CI: 1.7-3.2); moderate (OR 3.5, 95% CI: 2.6-4.7) and large (OR 5.8, 95% CI: 4.5-7.6). Waist loss had a protective effect on MetS (OR 0.6, 95% CI: 0.4-0.9). Waist gain showed a detrimental effect on all parameters of MetS in both genders, except for high-density lipoprotein cholesterol and fasting blood sugar in women. Conclusions: Waist gain, even mild, was a risk factor of the development of MetS and its parameters. Intervention for reducing WC could be an effective strategy to decrease incident MetS.