To determine if estimated glucose disposal rate (eGDR) can predict cardiovascular disease mortality risk at different levels of glycaemic tolerance. The eGDR levels of 11 656 individuals aged 45-79 years from the National Health and Nutrition Examination Survey cycles 1999 to 2010 were analysed. Associations between eGDR levels and all-cause and cardiovascular mortality were examined using Cox proportional hazards and Fine and Gray models, respectively. After a median follow-up of 12.8 years, a total of 2852 participants died, with 777 of those deaths attributed to cardiovascular causes. When comparing participants with eGDR values of ≤4 mg/kg/min to those with eGDR values falling within the ranges of 4-6, 6-8 and >8 mg/kg/min, it was found that the latter groups exhibited lower hazard ratios for both all-cause mortality (0.61 [0.52-0.72], 0.61 [0.52-0.72] and 0.46 [0.39-0.55]) and cardiovascular mortality (0.44 [0.33-0.57], 0.45 [0.34-0.59] and 0.30 [0.23-0.40]). A U-shaped relationship between eGDR and all-cause mortality was observed, with an inflection point at an eGDR of 9.54 mg/kg/min. In the general population, the association between reduced eGDR and all-cause and cardiovascular mortality was independently significant, contributing to the identification of individuals at high risk for different levels of glucose tolerances.