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Background: Hospital readmissions for acute exacerbation of chronic obstructive pulmonary disease (COPD) are one of the leading causes of healthcare expenditures worldwide. Objectives: To identify risk factors for hospital readmission in COPD patients. Methods:We prospectively evaluated 129 consecutive patients hospitalized for acute exacerbation of COPD. Clinical, spirometric and arterial blood gas variables were measured during hospitalization. Socioeconomic characteristics, comorbidity, dyspnea, functional dependence, depression, social support and quality of life were also analyzed. Readmission was defined as one or more hospitalizations in the following year. Results:During the follow-up period, 75 (58.5%) patients were readmitted. In bivariate analysis, readmission was associated with previous hospitalization for COPD in the past year, dyspnea scale, PaCO₂ at discharge, depression, cor pulmonale, chronic domiciliary oxygen and quality of life measured by the St. George’s Respiratory Questionnaire. In multivariate analysis, the best predictor of readmission was the combination of hospitalization for COPD in the previous year (odds ratio, OR: 4.27; 95% confidence interval, CI: 1.5–12), the total score of the St. George’s Respiratory Questionnaire ≧50 points (OR: 2.36; 95% CI: 1.03–5.04) and PaCO₂ at discharge ≧45 mm Hg (OR: 2.18; 95% CI: 0.84–5.06). With this model, the probability of readmission for patients without any of these variables was 7%, while it was 70% for the patients with all three variables present. Conclusion: The combination of quality of life, hospitalization for COPD in the previous year and hypercapnia at discharge are useful predictors of readmission at 1 year.