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This study aimed to analyze the impact of the residual cholesterol inflammatory index (RCII) and the triglyceride-glucose-body mass index (TyG-BMI) on the risk of cardio-cerebrovascular disease (CCVD). Data were obtained from the China Health and Retirement Longitudinal Study, and participants were categorized into 4 groups based on optimal cutoff values of RCII and TyG-BMI. The influence of RCII, TyG-BMI, and their combination on CCVD was assessed using Cox proportional hazards regression and Kaplan-Meier survival models. A total of 7677 individuals were included. Both higher RCII and higher TyG-BMI were independently associated with increased risk of CCVD. Importantly, the combined elevation of RCII and TyG-BMI showed the highest risk (HR = 1.47, 95% CI = 1.21-1.78, P < .05), whereas elevation of either marker alone was not statistically significant. Furthermore, no significant multiplicative or additive interaction between RCII and TyG-BMI was observed. These findings suggest that combined assessment of RCII and TyG-BMI may better identify high-risk individuals, although the lack of interaction indicates that the 2 indices contribute independently to CCVD risk.