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Background: Metabolic syndrome (MetS) is one of the world's largest health epidemics, and its management is a major challenge worldwide. The aim of this 10-year follow-up study was to assess the most important predictors of MetS persistence among an Iranian adult population. Methods: In this cohort study, 887 out of 2000 participants with MetS aged 20-74 years in the central part of Iran were followed-up for about 10 years from 2005-2006 to 2015-2016. MetS was defined based on the criteria of NCEP-ATP III adopted for the Iranian population. Cox proportional hazards regression was conducted to evaluate the predictors of MetS persistence in crude- and multivariate-adjusted models. Results: Our analyses showed that 648 out of 887 participants (73%) completed the follow-up and 565 (87.2%) of them had persistence of MetS after 10-year follow-up. There was a significant association between age, weight, body mass index, triglyceride, and waist circumference in participants who had MetS compared to those without MetS after 10-year follow-up (P < 0.05). There was a direct association between increases in the mean changes of systolic/diastolic blood pressure, waist circumference, and low HDL-C and risk of MetS persistence after adjusting the model for sex and age in the total population (Ptrend < 0.05). The trends were the same for women except in diastolic blood pressure. After adjustment for potential confounders, the risk of MetS persistence in men was significantly higher than women (HR = 1.98, 95% CI: 1.38-2.85, Ptrend = 0.001). Conclusions: Most of the risk factors of MetS were positively associated with persistence of MetS. Therefore, modification of lifestyle is recommended to reduce MetS. [ABSTRACT FROM AUTHOR]