The objective of this study was to test the psychometric properties of the QUALEFFO-41, an osteoporosis-specific health-related quality of life (HRQoL) measure, in a population sample. The study involved repeated administration of QUALEFFO-41 and another measure of HRQoL, the SF-36, to a stratified random population sample to test reliability and validity of instrument. The study was set in urban Harrow, Middlesex, UK and rural Cambridgeshire, UK. The participants were 83 males and 88 females aged 65-80+ years. Of the 230 individuals contacted 76.5% participated. The test-retest reliability of most QUALEFFO-41 items was good (Kappa 0.59-0.91) but two items had lower repeatability. Internal consistency was also generally good, but suggestive of some redundancy for three domains. The QUALEFFO-41 domains in general correlated well with SF-36 domains (r = 0.57 to r = 0.87), suggesting good validity. The QUALEFFO-41 has been shown to be a reliable and valid disease-specific HRQoL measure for osteoporosis. In population samples, it can be administered by post, or with a professional available to answer queries. Some specific items perform less well than may be desired and there is evidence of some redundancy, but further investigation is required and there are not yet grounds for textual change. We recommend continued use of this well-validated, reliable instrument.