The aim of this study is to identify the factors affecting mortality in patients with chronic obstructive pulmonary disease (COPD) hospitalized with exacerbation. A COPD cohort study was designed. Demographic data, the reason of mortality, Charlson co-morbidity index (CCI), COPD comorbidity index (COTE), age, dyspnea, airway obstruction (ADO) index, modified ADO index and dyspnea, airway obstruction, smoking, exacerbation (DOSE) index, and their relationship with mortality were investigated. One hundred and forty COPD patients hospitalized with exacerbation were included in the study. Eighty-seven (62.15%) of the patients were alive and 53 (37.85%) of them were deceased. The number of patients with CCI ≥ 7 was none in living patients and 11 (20.8%) in the deceased group (p<0.001). The percentage of treatment compliant patients during stable conditions was lower in the deceased group (p<0.001). ADO and COTE indices were significantly higher in the deceased group. There was no difference in modified ADO and DOSE scores between the groups. Multivariate analysis showed that lung cancer, CCI 7, hypoxemia (PaO2 <60 mmHg), and longer admission to the intensive care unit were independently associated with 3.4, 4.4, 2.1, and 3.0-fold mortality, respectively (p <0.05). Additionally, COTE ≥ 4 and noncompliance to regular COPD treatment were found to be associated with shorter survival in Kaplan Meier analysis (p<0.05). In conclusion, comorbidities and most notably lung cancer was associated with mortality in COPD. Also, high CCI and COTE index were risk factors for increased mortality.