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Background: A number of instruments have been developed to measure health-related quality of life (HRQoL), differing in the health domains covered and their scoring. Although few such measures have been consistently included in US national health surveys over time, the surveys have included data on a broad range of symptoms and impairments, which enables the tracking of population health trends., Objectives: To compare trends in HRQoL as measured using existing instruments versus using a broader range of symptoms and impairments collected in multiple years of nationally representative data., Data and Measures: Data were from the 2000-2010 Medical Expenditure Panel Survey, which is nationally representative of the noninstitutionalized US population. Level of and trends in HRQoL derived from a broad range of survey symptoms and impairments (SSI) was compared with HRQoL from the SF-6D, the HALex, and, between 2000 and 2003, the EuroQol-5D (EQ-5D) and EQ-5D Visual Analog Scale., Results: Trends in HRQoL were similar using different measures. The SSI scores correlated 0.66-0.80 with scores from other measures and mean SSI scores were between those of other measures. Scores from all HRQoL measures declined similarly with increasing age and with the presence of comorbid conditions., Conclusions: Measuring HRQoL using a broader range of symptoms and impairments than those in a single instrument yields population health trends similar to those from other measures while making maximum use of existing data and providing rich detail on the factors underlying change.