Background/aim: Exacerbations are key events in chronic obstructive pulmonary disease (COPD). Frequent exacerbations occurring during the natural course of COPD lead to deterioration of health-related quality of life and are major causes of morbidity and mortality. The aim of this study was to identify factors independently associated with frequent severe exacerbations of COPD that require hospitalization. Materials and methods: A case-control study was performed to analyze risk factors and frequency of severe exacerbations, which were defined by the GOLD guideline criteria. Stepwise multivariate regression was used to determine the significant predictors of frequent exacerbations. Results: Results revealed five independent predictors of frequent exacerbations: age, length of hospital stay, FEV1/FVC ratio, CRP level above 10 mg/L, and respiratory comorbidities. Conclusion: COPD patients should be more carefully assessed in terms of age, length of hospital stay, FEV1/FVC ratio, CRP level, and respiratory comorbidities. Patients under 65 years of age with respiratory comorbidities, longer hospital stay, lower FEV1/FVC ratio and CRP of <10 mg/L are more prone to experiencing a minimum of one additional hospitalization in the following year. Patients could spend less time in the hospital environment and increase their quality of life by adjusting these risk factors for hospitalization due to COPD.