Our aim was to assess the impact of comorbidities on existing COPD prognosis scores.A total of 543 patients with COPD (FEV1 <80% and FEV1/FVC <70%) were included between January 2003 and January 2004. Patients were stable for at least 6 weeks before inclusion and were followed for 5 years without any intervention by the research team. Comorbidities and causes of death were established from medical reports or information from primary care medical records. The GOLD system and the body mass index, obstruction, dyspnea and exercise (BODE) index were used for COPD classification. Patients were also classified into four clusters depending on the respiratory disease and comorbidities. Cluster analysis was performed by combining multiple correspondence analyses and automatic classification. Receiver operating characteristic curves and the area under the curve (AUC) were calculated for each model, and the DeLong test was used to evaluate differences between AUCs. Improvement in prediction ability was analyzed by the DeLong test, category-free net reclassification improvement and the integrated discrimination index.Among the 543 patients enrolled, 521 (96%) were male, with a mean age of 68 years, mean body mass index 28.3 and mean FEV1% 55%. A total of 167 patients died during the study follow-up. Comorbidities were prevalent in our cohort, with a mean Charlson index of 2.4. The most prevalent comorbidities were hypertension, diabetes mellitus and cardiovascular diseases. On comparing the BODE index, GOLDABCD, GOLD2017 and cluster analysis for predicting mortality, cluster system was found to be superior compared with GOLD2017 (0.654 vs 0.722, P=0.006), without significant differences between other classification models. When cardiovascular comorbidities and chronic renal failure were added to the existing scores, their prognostic capacity was statistically superior (P<0.001).Comorbidities should be taken into account in COPD management scores due to their prevalence and impact on mortality.