INTRODUCTION: Although recognition of insulin sensitivity as a risk factor for cardiovascular disease is growing, a deeper understanding of its role is impeded by the cost and complexity of currently available measures. This report evaluates previously described alternative indices of insulin sensitivity with the goal of identifying a reliable, but logistically simpler, alternative. METHODS: Data from 1460 participants in the Insulin Resistance Atherosclerosis Study (IRAS) were used to assess the proportion of the relationship between a recognized measure of insulin sensitivity (Bergman's S1) and cardiovascular risk factors that is contained in each of nine alternative measures. RESULTS: A number of the alternative indices contained a substantial proportion of the information available in Bergman's S1. The Galvin's index and the homeostasis model were most promising. However, there remained a significant amount of the information in Bergman's S1 that was not contained in any of the alternative indices. DISCUSSION: There are simpler alternative indices of insulin sensitivity for use in epidemiological studies, but each alternative is associated with some loss of information. It may be possible that this loss can be overcome with an increased sample size; however, using the alternative indices may also confound the assessment of insulin sensitivity with other underlying factors (i.e., hyperinsulinemia). The alternative indices are not recommended for the clinical assessment of insulin sensitivity for an individual patient or subject.