Objective To investigate the relationship between estimated glucose disposal rate (eGDR) and the incidence of cardiovascular disease (CVD) in individuals without diabetes and those with diabetes. Methods Participants were drawn from the China Health and Retirement Longitudinal Study from 2011 to 2018. Participants were divided into four subgroups based on quartiles of baseline eGDR. In this study, data were analyzed using Kaplan-Meier survival curves, Cox proportional hazards models, restricted cubic spline curves, subgroup analyses, and receiver operator characteristic curves. Results A total of 6 283 participants were included. Among them, 47.2% are male, with an average age of (59.6±9.5) years; 285 cases (4.5%) had diabetes; there were 1 571 cases in Q1 group, 1 572 cases in Q2 group, 1 583 cases in Q3 group, and 1 557 cases in Q4 group. A total of 761 CVD events occurred. According to the multivariate-adjusted model, baseline eGDR levels were significantly associated with the risk of CVD events (P<0.05). Baseline eGDR was associated with the risk of CVD events in individuals without diabetes (P<0.05), but the results were not entirely consistent for those with diabetes [CVD: hazard ratio (HR)=0.85, 95% confidence interval (CI) (0.75, 0.96), P=0.012; heart disease: HR=0.91, 95%CI (0.78, 1.06), P=0.211; stroke: HR=0.74, 95%CI (0.58, 0.93), P=0.012]. Restricted cubic spline curves revealed significant negative linear relationships between baseline eGDR and CVD, heart disease, and stroke. Subgroup analyses with interaction testing revealed that the association between baseline eGDR and CVD was not modified by age, sex, smoking status, alcohol consumption, or dyslipidemia. Receiver operator characteristic curves further demonstrated that baseline eGDR exhibited significantly better predictive performance than the triglyceride-glucose (TyG) index, obesity indices, and the TyG index-obesity composite. Conclusions Low level baseline eGDR is associated with an increased risk of CVD in individuals without diabetes. This finding may help improve risk stratification to guide preventive measures and enhance the prognosis of CVD.