This study aimed to evaluate the role of the triglyceride (triacylglycerol) glucose (TyG) index in predicting and mediating the development of cardiovascular disease (CVD). This cohort study included 6078 participants aged over 60 years who participated in a routine health check-up programme from 2011 to 2017. The competing risk model, cox regression model and multimediator analyses were performed. TyG was calculated as ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. During a median 6 years of follow-up, 705 (21.01/1000 person-years) CVD events occurred. In fully adjusted analyses, quartiles 3 and 4 versus quartile 1 of TyG index (adjusted subhazard ratios [SHRs] 1.33 [95% CI: 1.05-1.68] and 1.72 [1.37-2.16]) were associated with an increased risk of CVD events. The continuous time-dependent TyG remained significant in predicting CVD events (adjusted hazard ratios [HR] 1.43 [1.24-1.63]). The adverse estimated effects of body mass index (BMI) or resting heart rate (RHR) on CVD mediated through the joint effect of the baseline and follow-up TyG index. In addition, an effect mediated only through the follow-up TyG existed (P < 0.05). Thus, it is necessary to routinely measure the TyG. The TyG index might be useful for predicting CVD events in clinical practice.