Introduction: The metabolic syndrome includes risk factors for non-communicable diseases such as central obesity, hyperglycemia, dyslipidemia and hypertension accompanied by pro-inflammatory and hypercoagulability states. The aim of this study was to determine the effects of weight change on incident metabolic syndrome. Materials and Methods: This was a prospective cohort study, the population of which included all participants of the TLGS, phases one and two, >20 yrs and above, free of metabolic syndrome, based on the Iranian waist circumference, and NHLBI. Iranian waist circumference was defined with different cutoff points, according to cross sectional and outcome-based studies. Data was obtained by interviews, questionnaires, observation, and physical and laboratory examinations.The incidence of metabolic syndrome after 3.1 years of follow up was determined. Percent of weight change (PWC) was divided in five quintiles. Using the logistic regression test, odds ratio and 95% confidence interval of incident metabolic syndrome and its components for these quintiles, after adjusting for confounders, were calculated. Results: Age adjusted incidences of metabolic syndrome after a 3.1 year follow up, according to Iranian WC outcome were 20.6% (males 26%, females 20.9%) and for Iranian WC cross sectional and NHLBI were 26.2% (males 34.4%, females 26.1%) and 23.7% (males 24.4%, females 29.4%) respectively. For both genders, based on Iranian W.C and NHLBI, a weight reduction of at least 1.3%, compared to baseline, in women had a protective effect against incident metabolic syndrome. In men a weight gain of at least 1.4% since baseline resulted in an increase in the odds ratio. In women, weight gain of at least 1.3% since baseline, based on the Iranian WC cross sectional, NHLBI and at least 4% based on Iranian W.C-outcome resulted in progressive incidence of metabolic syndrome. These reductions of at least 1.3% in males and 2.5% in females, decreased the relative risk of abdominal obesity, but had no effect on other components of metabolic syndrome, including: hypertriglyceridemia, low HDL, hyperglycemia, and hypertension. Although in both sexes, increase in weight resulted in abdominal obesity, the cut off points according to various definitions were different. Conclusion: Considering the preventive effect of weight loss against incident metabolic syndrome and abdominal obesity, we recommend educational programs to enhance awareness regarding overweight and obesity and motivate individuals to lose weight.