Abstract: Objective To explore the relationship between triglyceride-glucose (TyG) index and clustering of cardiovascular risk factors in adolescents. Methods A total of 1 777 residents from Longzihu area in Bengbu, Anhui Province were selected by random sampling. Questionnaires, physical examination and laboratory measurements were used to collect general and clinical information. TyG index was grouped by quartiles. Logistic regression analysis was performed to analyze the relationship between TyG index and cardiovascular risk factors clustering. Using ROC curve analysis, the cut-off value and clinical significance of cardiovascular risk factors clustering prediction by TyG index were calculated for comparison with other indicators. Results The survey included total 748 males (42.09%) and 1 029 females (57.91%) with the average age of (60.82±11.24) years. Spearman correlation analysis showed that TyG index were significantly correlated with cardiovascular disease risk factors (all P<0.001). Indeed, multivariate Logistic analysis showed that TyG index was a risk factor for cardiovascular disease risk factors clustering (OR=2.930, 95% CI:2.625-3.272). When the TyG index was 8.78, the Youden index of cardiovascular disease risk factors clustering determination by TyG index was the maximum. The area under the receiver operator characteristic curve (ROC) curve of TyG index was significantly different from that of fasting blood glucose, triglycerides and body mass index (BMI) (all P<0.05). However, no significant difference was observed when compared with waist-to-height ratio (WHtR) (Z=0.117, P=0.907). Conclusions There is a significant correlation between TyG index and clustering of cardiovascular risk factors, suggesting that TyG index may be applied as a simple marker for identifying adolescents with clustering of cardiovascular risk factors.