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Background: Co-morbidity is a powerful predictor of health care outcomes and costs, as well as an important cofounder in epidemiologic studies. The effect of co-morbidities is generally related to mortality or complications. This study evaluated the association between co-morbidity and health-related quality of life (HRQoL) in patients awaiting total joint replacement. Methods: A total of 893 patients were recruited to the study between August 2002 and November 2003 in four Finnish hospitals. The effect of co-morbidity on HRQoL was measured by the generic 15D instrument and by a Visual Analog Scale (VAS). Comparative variance analysis of socio-demographic and clinical characteristics was described by using either an independent samples t-test or the Chi-square test. The differences in each of the 15D dimensions and the overall 15D single index score for patients were calculated. Two-sided p-values were calculated with the Levene Test for Equality of Variances. Results: Patients with co-morbidity totaled 649; the incidence of co-morbidity was 73%. The mean number of co-morbidities among the patients was two. At baseline the 15D score in patients with and without co-morbidity was 0.778 vs 0.816, respectively. The difference of the score (0.038) was clinically and statistically significant (P < 0.001). The patients' scores with and without co-morbidity on the different 15D dimensions related to osteoarthritis-moving, sleeping, usual activities, discomfort and symptoms, vitality and sexual activity–were low in both groups. Patients with co-morbidity scored lower on the dimensions of moving, vitality and sexual activity compared to the patients without co-morbidity. Comorbidity was significantly associated with a reduced HRQoL. Patients without co-morbidity had poorer VAS, arthritis had strong effect to their quality of life compared to the patients with co-morbidity. Conclusion: Assessing co-morbidity in patients placed on the waiting list for joint replacement may be useful method to prioritization in medical decision-making for healthcare delivery. The assessment of comorbidities during waiting time is important as well as evaluating how the co-morbidity may affect the final outcomes of the total joint replacement. Published: 15 March 2007 Health and Quality of Life Outcomes 2007, 5:16 doi:10.1186/1477-7525-5-16 Received: 5 February 2007 Accepted: 15 March 2007 This article is available from: http://www.hqlo.com/content/5/1/16 © 2007 Tuominen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.