OBJECTIVES: Generic health measures are routinely used to assess HRQoL in population studies of persons with diabetes and other chronic illness.  It is not known whether these measures provide consistent results in assessing HRQoL in patients with diabetes or whether these measures are able to discriminate between the HRQoL of persons with and without diabetes and across levels of diabetes severity.  To compare HRQoL differences across levels of diabetes severity using six generic indexes and to examine the generic indexes ability to discriminate between the HRQoL levels across diabetes severity. METHODS: The National Health Measurement Study is a population-based, cross-sectional survey of 3844 non-institutionalized adults in the United States.  Participants completed six generic measures of HRQoL—EQ-5D, HUI2, HUI3, QWB-SA, SF-36v2 (yielding PCS, MCS, and SF-6D), and HALex.  Diabetes severity was classified as non-diabetic, diabetes without medication, diabetes with medication, and diabetes with insulin.  Weighted mean difference scores between each diabetes category adjusted for age, sex, and gender were calculated for each index.  Effect sizes were calculated for each index between each diabetes group by standardizing to the population standard deviation among those without diabetes. RESULTS: A total of 726 (19%, unweighted) individuals self-reported diabetes.  Across all indexes persons with diabetes demonstrated statistically significantly lower unadjusted and adjusted HRQoL scores than those without diabetes (p <0.001).    The HALex had the highest effect sizes for all comparisons between diabetes categories (ranging from 0.16 through 1.30), followed by the SF-36v2 PCS (ranging from 0.24 through 0.98), and the SF-36v2 MCS (ranging from 0.06 through 0.57).  CONCLUSIONS: Results demonstrate the ability for generic HRQoL indexes to differentiate between persons with and without self-reported diabetes.  The HALex was consistently better at differentiating among diabetes severity as.  This study indicates that generic indexes are useful for evaluating HRQoL even in a diabetes-specific context.