ABSTRACT: Evidence for the association between the frailty index and cardiovascular disease (CVD) is inconclusive, and this association has not been evaluated in Chinese adults. We aim to examine the association between the frailty index and CVD among middle-aged and older Chinese adults. We conducted cross-sectional and cohort analyses using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). From 2011 to 2018, 17,708 participants aged 45 years and older were included in the CHARLS. The primary outcome was CVD events (composite of heart disease and stroke). Multivariable adjusted logistic regression and Cox proportional hazards models were used to estimate the association between the frailty index and CVD in cross-sectional and follow-up studies, respectively. A restricted cubic spline model was used to characterize dose-response relationships. A total of 16,293 and 13,580 participants aged 45 years and older were included in the cross-sectional and cohort analyses, respectively. In the cross-sectional study, the prevalence of CVD in robust, pre-frailty and frailty was 7.83%, 18.70% and 32.39%, respectively. After multivariable adjustment, pre-frailty and frailty were associated with CVD; ORs were 2.54 (95% confidence interval [CI], 2.28-2.84) and 4.76 (95% CI, 4.10-5.52), respectively. During the 7 years of follow-up, 2122 participants without previous CVD developed incident CVD; pre-frailty and frailty were associated with increased risk of CVD events; HRs were 1.53 (95% CI, 1.39-1.68) and 2.17 (95% CI, 1.88-2.50), respectively. Furthermore, a stronger association of the frailty index with CVD was observed in participants aged <55, men, rural community-dwellers, BMI ≥ 25, without hypertension, diabetes or dyslipidemia. A clear nonlinear dose-response pattern between the frailty index and CVD was widely observed (p < 0.001 for nonlinearity), the frailty index was above 0.08, and the hazard ratio per standard deviation was 1.18 (95% CI 1.13-1.25). We observed the association between the frailty index and CVD among middle-aged and elderly adults in China, independent of chronological age and other CVD risk factors. Our findings are important for prevention strategies aimed at reducing the growing burden of CVD in older adults.