Abstract The chronic lymphocytic leukemia comorbidity index (CLL-CI) is an efficient, CLL-specific tool derived from the Cumulative Illness Rating Scale. The CLL-CI is based on the assessment of the organ systems found to be most strongly associated with event-free survival (EFS) in CLL: vascular, upper gastrointestinal, and endocrine, at the time of initiation of CLL therapy. The CLL-CI categorizes patients into low, intermediate, and high risk groups. In the present study, we have employed the CLL-CI in a population-based cohort comprising 4975 patients with CLL. We demonstrate that CLL-CI retains prognostic significance in this large cohort and is associated with overall survival (OS) and EFS from time of first therapy. Furthermore, CLL-CI associates with OS, EFS, and time to first treatment from diagnosis independently of the CLL International Prognostic Index. These findings support the use of the CLL-CI both in research and in clinical practice.