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BACKGROUND AND AIM: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide, and the majority of patients have at least one comorbid condition of clinical significance. Therefore, we studied its prevalence and implication based on experience from the Republic of Moldova. METHODS: The study was a prospective cohort study that included 435 patients with COPD from 2015 to 2017. RESULTS: We found heart failure in 38.62% of the patients, hypertension in 50.11%, coronary artery disease in 23.45%, diabetes mellitus in 10.11%, renal failure in 1.15%, rheumatoid arthritis in 3.22%, depression in 4.83%, cognitive impairment in 4.37%, obesity in 29.89%, and cachexia in 3.22%. Only 24.65% of patients did not have comorbidities. One comorbidity was found in 23.73%, two in 24.19%, three or more in 27.42%. The Charlson comorbidity index (CCI) had a medium negative correlation with the 6-minute walking test (r=–0.37, p<0.001) and a weak correlation with the rate of exacerbations (r=0.17, p=0.016). CCI had a strong correlation with ADO (age, dyspnea and airflow obstruction) (r=0.75, p<0.001); moderate with BODE (body mass index, airflow obstruction, dyspnea, and exercise) (r=0.3, p<0.001); and weak with BODEx (body mass index, airflow obstruction, dyspnea, and exacerbations), CODEX (comorbidity, obstruction, dyspnea, and previous severe exacerbations), and DOSE (dyspnea, obstruction, smoking, and exacerbation). CCI had a medium correlation with St. George’s Respiratory Questionnaire (SGRQ) activity (r=0.36, p<0.001), impact (r=0.34, p<0.001), and total (r=0.37, p<0.001) scores, and the overall quality of life assessed by SGRQ and Clinical COPD Questionnaire. CONCLUSIONS: Patients with COPD require a multidisciplinary approach to assess and manage a variety of conditions, which influence the evolution and prognosis of COPD. Patients often have one or two comorbidities of clinical significance, and they are predominantly cardiovascular and metabolic. Patients with comorbidities tend to have a poorer health-related quality of life. Comorbidities can be assessed by multidimensional indexes such as ADO and BODE. [ABSTRACT FROM AUTHOR]