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Background: Health-related quality of life (HRQL) deficits associated with diabetes are likely not limited to the condition itself, but may be attributable to other factors including treatment, complications and comorbid medical conditions. Using generic measures to explore HRQL deficits in diabetes is appropriate, asdiabetes specific measures may not capture the additional HRQL deficits associated with comorbidities. Objectives: The purpose of this analysis was to assess the impact of comorbid heart disease, stroke and arthritis on HRQL in people with diabetes in the Canadian population using the Health Utilities Index Mark 3 (HUI3), a generic preference-based measure of HRQL. Methods: Data used in this analysis were collected as part of the 1996-1997 National Population Health Survey (NPHS Cycle 2). The sample was restricted to respondents over the age of 18. HRQL was assessed using the HUI3, which provides an overall index score, as well as single attribute utility scores for vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain and discomfort. Respondents were classified into 1 of 16 groups based on the presence or absence of diabetes, heart disease, stroke, and arthritis in all possible combinations. Analysis of covariance was performed for each single attribute and the overall HUI3 score, with determinants of health and proxy status included as covariates. The abbreviated model (N=66093) included sentinel medical conditions, sex, age in a quadratic form, education and number of medical conditions as covariates. The full model (N=39772) included total annual household income, body mass index (BMI), marital status, smoking status and proxy response status as covariates, in addition to the covariates of the abbreviated model. Results: Missing data on the determinants of health created systematic bias in the full model, so we opted to rely on the abbreviated model to address our primary objective. Overall HUI3 scores for respondents with heart disease (0.89, 95% CI: 0.88-0.90, p < 0.001) and diabetes (0.88, 95% CI: 0.87-0.89, p < 0.001) alone were similar, and both were statistically significantlylower than controls (i.e. respondents who did not have diabetes, heart disease, arthritis, or stroke) (0.92: 95% CI: 0.92-0.92). Stroke alone was the single medical condition associated with the largest burden (0.74, 95% CI: 0.72-0.76, p < 0.001). Regardless of the specific comorbidity, there was a general trend such that pairwise combinations of the four conditions were associatedwith decrements of overall HRQL of approximately 0.13 to 0.15 and tripletswere associated with decrements of approximately 0.26 to 0.30 compared to the control group. Overall HUI3 scores for diabetes in combination with heart disease (0.77), arthritis (0.78) or stroke (0.79) were considerably lower than diabetes alone (0.88). Of the single sentinel conditions, stroke was associated with the largest deficits on the cognition, ambulation and vision attributes. Arthritis was the single sentinel condition associated with the largest deficit on the pain attribute. Conclusions: From this analysis, it was apparent that across the general population aged 18 and over, the illness burden experienced by individuals with diabetes was not only associated with diabetes itself, but also with comorbid medication conditions. The HUI3, appeared to be useful for assessing HRQL in the sentinel medication conditions explored in this analysis, and useful for assessing the additional decrements in HRQL that occur when these conditions exist as comorbidities.