OBJECTIVES We aimed to validate the multi-attribute health utility (MAHU) derived from the CAT-5D-QOL, a computer-adaptive instrument composed of 5 domains (Walking, Handling Objects, Daily Activities, Pain/Discomfort, and Feelings) in people with self-reported osteoarthritis (OA), and to compare it with WOMAC_HUI3, the utility derived from the standard disease-specific measure in OA. METHODS Data were collected from participants (age 50+) who completed questionnaires CAT-5D-QOL in two waves and WOMAC in one wave of a Canada-wide online survey. To assess construct validity, we used multivariable regression to examine the associations between utilities and self-rated general health (GH, on a 5-point Likert scale), presence of several co-morbid conditions, and use of drugs. We assessed the responsiveness of CAT-5D-QOL by comparing changes in MAHU scores with changes in GH (anchor variable) between the two waves of the survey. RESULTS There was a strong correlation (Pearson r=0.77, n=520) between MAHU and WOMAC_HUI3 but the mean MAHU was significantly lower (0.79 vs. 0.86). No ceiling or floor effect was observed for either utility. Compared to WOMAC_HUI3, regression analysis demonstrated generally stronger association for MAHU with the number of analgesic drugs taken and self-reported GH scores. MAHU also showed significant associations with the presence of back pain, depression, ulcer, and cancer, whereas WOMAC_HUI3 correlated only with back pain. In the analysis of responsiveness, differences in mean MAHU scores were in the expected direction and significantly different for each level of change in GH scores. CONCLUSIONS MAHU and WOMAC_HUI3 were highly correlated and neither measure had a ceiling or floor effect. However, MAHU demonstrated better discriminative ability with respect to several health-related variables. MAHU was also sensitive to changes in overall health over time. These are all desirable properties for capturing the health impact of OA (and other conditions) and estimating cost-effectiveness of health interventions.