The triglyceride-glucose index (TyG index) is a validated measure of insulin resistance that reliably predicts Metabolic Syndrome (MetS) type 2 diabetes (T2DM) and premature atherosclerotic cardiovascular diseases (ASCVD). It includes measures of carbohydrate and lipid metabolism. We postulated that glycated hemoglobin (HbA1c), which in contrast to fasting glucose, reflects glycemic status over 2–3 months and not at a single time of day, may serve as a superior biomarker of MetS when combined with plasma triglycerides as the Ty-HbA1c index. Using data from a large cohort of American adults (n = 5039) in the National Health and Nutrition Examination Survey (NHANES) study, we compared the Ty- HbA1c and TyG index in predicting prevalent MetS, a harbinger of both T2DM and ASCVD. In this cohort, 22% of patients had MetS and the TyG and Ty- HbA1c indices were significantly increased in patients with MetS. Although both indices showed very good prediction performance on the prevalent of MetS, the TyG index had a significantly superior prediction as indicated by the Receiver Operating Characteristic (ROC) Area under the curve (AUC). Moreover, this significance was consistent across the 3 race groups. In the prediabetes subgroup, the ROC-AUC for TyG index was significantly higher than the Ty- HbA1c index. In conclusion, this cross-sectional study shows that the Ty-HbA1c index is not superior to the well-accepted TyG index in predicting MetS, a proxy of cardio-metabolic disorders in this large study of American adults. Furthermore, given that the TyG index is based on only fasting TG and glucose levels, it is more cost-effective.