Context: Deterioration of metabolic syndrome (MetS) has been associated with short telomere length (TL). Large-scale longitudinal studies with repeated measures of MetS and TL are lacking. Objectives: We examined whether baseline MetS components predict TL over time, and whether deteriorations in MetS parallel telomere attrition. Design and Setting: Participants were part of The Netherlands Study of Depression and Anxiety, an ongoing prospective cohort study. Participants: This study included 1808 participants age 18-65 years. Main Outcome Measures: Leukocyte TL (using qPCR) and MetS components (waist circumference, triglycerides, high-density lipoprotein [HDL] cholesterol, systolic blood pressure, and fasting glucose) were determined at baseline and after 6 years. Generalized estimated equation models were used to examine the associations between baseline MetS and TL over time, and linear regressions were used to associate 6-year changes in both MetS components and TL, while adjusting for sociodemographic and lifestyle factors. Results: Higher baseline waist circumference (B = -29.7; P = .006) and glucose (B = -26.4; P = .02), and lower HDL (B = 25.5; P = .03) were consistently associated with shorter TL over followup. Greater 6-year increase in waist circumference was associated with larger telomere attrition (B = -41.8; P = .01), and similar but nonsignificant associations were observed for larger increase in triglycerides and glucose levels. Conclusions: Metabolic dysregulations are associated with shorter telomeres over two time points. In particular, increasing abdominal adiposity is accompanied by accelerated telomere attrition. Future studies should elucidate underlying mechanisms of this bidirectional relationship and investigate whether targeting obesity may reduce telomere attrition to prevent further deterioration toward cardiovascular and aging-related complications.