Context and Objective. The purpose of this study was to determine optimal waist circumference (WC) cut-off values for the detection of multiple risk factor aggregation in individuals from Maracaibo, Venezuela. Participants and Methods. A total of 1,902 adult individuals of both genders belonging to MMSPS were included. Complete physical, laboratory, and anthropometric examination were done to evaluate Metabolic Syndrome (MS) components and insulin resistance. ROC curves were plotted for risk factor aggregation in order to assess WC cut-off point. Logistic regression models were constructed to assess risk factors associated with the WC. Results. There were 52.2% females and 47.8% males, with WC of 90.7±13.7 cm and 98.2±15.9 cm, respectively. ROC curves exhibited a WC cut-off point for women of 90.25 cm (68.4% sensitivity, 65.8% specificity) and 95.15 cm (71.1% sensitivity, 67.4% specificity) for men. HOMA2-IR and high blood pressure were associated with a WC over these cut-off points, as well as 2.5-fold risk increase for multiple risk factor aggregation (OR 2.56; CI 95%: 2.05–3.20; P