Abstract: Objective: To explore the association between estimated glucose disposal rate（eGDR） and the risk of cardiovascular disease（CVD） in middle-aged and elderly patients with metabolic syndrome（MS） using data from the China Health and Retirement Longitudinal Study（CHARLS） database. Methods: The middle-aged and elderly MS patients without CVD at baseline were selected from the CHARLS database as the participants. They were divided into three groups（group T1, group T2 and group T3） based on the tertiles of the natural logarithm of eGDR ln（eGDR）, with the lowest tertile as the reference. Multivariate Cox regression analysis was used to evaluate the association between eGDR and the incident CVD. A multivariable-adjusted restricted cubic spline（RCS） model was applied to assess the dose-response relationship. Results: A total of 1,154 MS patients were included, with a median follow-up of 108 months, and 300 patients（26.00%） developed new-onset CVD. Multivariate Cox regression analysis showed that after adjusting for confounding factors, each one-unit increase in eGDR on the logarithmic scale was associated with a 66% reduction in CVD risk（HR=0.34, 95% CI: 0.13-0.94, P=0.037）. RCS analysis indicated a significant linear negative association between eGDR and CVD risk(P_overall<0.001, P_nonlinea=0.968). Subgroup analyses revealed no significant interactions(P_{for interaction}>0.05), suggesting a consistent association across subgroups stratified by age, sex, and comorbidities. After incorporating eGDR, the area under the curve（AUC） of the base predictive model increased from 0.635 to 0.641（P=0.045）. Conclusion: Among middle-aged and elderly patients with MS, a higher eGDR level is associated with a lower risk of the incidence of CVD. As a simple and non-invasive marker for assessing insulin resistance, eGDR may contribute to the assessment of CVD risk in middle-aged and elderly populations, but its clinical utility still needs further validation through prospective studies.