The aim of this study was to determine optimal cut-off points for fasting and post-glucose stimulus surrogates of insulin resistance to predict metabolic syndrome in adolescents according to several definitions. One hundred fifty-five adolescents living in Mexico City were enrolled during 2011 and 2012. Waist circumference and blood pressure were recorded. Subjects received an oral glucose load of 1.75 g per kg up to a maximum dose of 75 g. Blood samples were drawn at baseline and 120 minutes. Concentrations of plasma glucose, triglycerides, high-density lipoprotein cholesterol and insulin were determined. The frequency of metabolic syndrome showed a large variability when using a variety of published definitions; in contrast, the optimal cut-off points for fasting insulin, homeostatic model assessment of insulin resistance and two-hour oral glucose tolerance test insulin were very similar in almost all the definitions considered and had adequate diagnostic performance: area under the curve >0.869, sensitivity >0.835 and specificity >0.755. Insulin resistance surrogates had substantial agreements with Ford, Cook and Salas definitions (Kappa~0.62; agreement~82%); moderate agreement was observed for International Diabetes Federation, Cruz and Ferranti definitions (Kappa~0.41–0.59; agreement~77%). Insulin resistance surrogates may be a better approach for metabolic syndrome assessment in an adolescent population because of reduced variability and a higher predictive value.