Objective To explore the association between triglyceride glucose-waist circumference (TyG-WC) index and the risk of stroke among the middle-aged and older people, and compare the differences among TyG-WC, triglyceride glucose (TyG), and waist circumference (WC) in the prediction of stroke. Methods The data of adults aged 45 years or older enrolled in the China Health and Retirement Longitudinal Study registry in 2011 were collected, and the endpoint was self-reported or physician-diagnosed new stroke event by 2015. According to the baseline TyG-WC tertile, individuals were divided into three groups: TyG-WC tertile 1, tertile 2, and tertile 3 groups. Multiple logistic regression analyses were performed to analyze the associations of TyG-WC, TyG, and WC with the risk of stroke. The area under the curve (AUC) of receiver operating characteristic (ROC) curve, integrated discrimination improvement (IDI) score, and net reclassification improvement (NRI) score were calculated to evaluate the predictive value of TyG-WC, TyG, and WC in stroke. Results A total of 5847 participants were finally included, with 1949 in each group. After 4 years of follow-up, there were 252 cases of new stroke. There was significant difference in the incidence of stroke among the three groups (TyG-WC tertile 1 group: 2.57%, TyG-WC tertile 2 group: 4.16%, TyG-WC tertile 3 group: 6.21%; P<0.05). The results of multiple logistic regression analyses showed that the risk of new stroke in the third tertile group of TyG-WC and WC was higher than that in the first tertile group, respectively [TyG-WC: odds ratio (OR)=1.465, 95% confidence interval (CI) (1.033, 2.078), P=0.032; WC: OR=1.717, 95%CI (1.190, 2.478), P=0.004], while TyG was not the risk factor of stroke (P>0.05). The ROC curve analysis showed that the AUC of WC (0.566) was slightly higher than that of TyG-WC (0.556) and TyG (0.527). The IDI of TyG-WC (0.25%) was slightly higher than that of WC (0.22%), and the both were higher than that of TyG (0.07%). The NRI of WC (25.04%) was slightly higher than that of TyG-WC (19.68%), and the both were high than that of TyG (12.02%). Conclusions Compared with TyG, higher TyG-WC and WC are associated with the increased risk of new stroke among the middle-aged and older people. The predictive value of TyG-WC and WC for the risk of new stroke in the middle-aged and elderly is similar, and is better than that of TyG.