Comorbid conditions have rarely been systematically studied among patients with myelodysplastic syndromes (MDS). We conducted a large population-based study to assess the role of comorbidity in the survival of newly diagnosed MDS patients. This study included 1708 MDS patients (age > or =66 years) diagnosed in the US during 2001-2002, with follow-up through the end of 2004. Hazard ratios (HRs) were estimated using multivariate Cox proportional hazard models. The median survival time was approximately 18 months. Fifty one percent of MDS patients had comorbid conditions. Patients with comorbid conditions had significantly greater risk of death than those without comorbidities. The HR was 1.19 (95% confidence interval (CI): 1.05-1.36) and 1.77 (95% CI: 1.50-2.08) for those with a Charlson index of 1-2 and > or = 3, respectively. The risk of death increases with Charlson index. MDS patients who have congestive heart failure or chronic obstructive pulmonary disease had significantly shorter survival than patients without those conditions, whereas diabetes did not appear to have an impact on survival. This study confirms comorbidity as a significant and independent determinant of MDS survival, and the findings underscore the importance to take comorbid conditions into account when assessing the prognosis of MDS.