OBJECTIVES: Comorbidities can influence generic measurement of health by multi-attributes or indirect utility. We investigated the impact of comorbidities to assess indirect utility with the Medical Outcomes Study Short Form 6D (SF-6D) measuring health-related quality of life in patients with osteoarthritis (OA). METHODS: The 878 patients, aged 45-75 years with symptomatic knee or/and hip, of the KHOALA (Knee and Hip OsteoArthritis Long term assessment) cohort were included in the study. Comorbidities were assessed by the Functional Comorbidity Index (FCI) and grouped in 9 categories. Limitation in activities and pain was measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).Two separate linear regression models, using the number of comorbidities or the different categories of comorbidities of the FCI, were fitted to determine predictors of utility score. RESULTS: For the 878 patients included, the mean (SD) utility score was 0.66 (11; range 0.32–1.00) and mean number of comorbidities 2.05 (1.58). In the first multivariate model, , for each additional comorbidity (range 0–9) the mean utility score decreased of 0.01 point (beta= -0.010, p<0.0001). In the second model, including comorbidities by categories, only psychiatric disease (beta=-0.043, p<0.0001) and degenerative disc disease (beta=-0.014, p=0.018) predicted low utility score. In both regression models a worsened function (increased WOMAC function score) significantly decreased the utility score. The number of comorbidities explained 2% of the variance in utility score (partial R-square=0.02) and psychiatric and degenerative disc diseases explained 2% (partial R-square=0.025) and 0.7% (partial R-square=0.007), respectively, of the variance in utility score, whereas the WOMAC function score explained 38% of the variance in both models (partial R-square = 0.38). CONCLUSIONS: Compared to greater negative effect of functional impairment, comorbidities have a negative but relatively marginal impact on indirect utility score. This suggests that clinically, considering the functional severity of OA remains a first priority.