Insulin resistance is supposed to be the basis of metabolic syndrome (MS), although it is difficult to measure. The ratio of triglyceride (TG) to high-density lipoprotein (HDL) has been proposed as a surrogate marker of insulin resistance in overweight subjects. The aim of the present study was to assess the accuracy of the TG/HDL ratio for the diagnosis of MS. Data of 18,778 active workers (77.6% men) enrolled in 3 insurance companies in Spain were collected from their annual health examinations. Mean age was 42.2 +/- 10.7 years. MS was assessed according to modified Adult Treatment Panel III criteria. Prevalences of MS were 18.8% in men and 6.1% in women. Mean value of the TG/HDL ratio was 2.50 +/- 2.2 and increased in parallel to the number of MS components present. Subjects with MS had a ratio that was 2 times higher compared with those without (5.10 vs 2.03, p <0.001). Receiver operating characteristic curves were performed to assess the capability of the TG/HDL ratio to contribute to a diagnosis of MS and 80% sensitivity and 78% specificity were obtained for values >2.75 in men and >1.65 in women. In conclusion, the TG/HDL ratio is a feasible and accurate measurement for assessment of MS in healthy subjects. We propose cut-off values of 2.75 for men and 1.65 for women for a diagnosis of MS.