Background: Multiple hospitalizations for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with considerable morbidity and mortality. Objectives: To identify predictive factors of multiples hospitalizations for AECOPD. Methods: This is a retrospective single center study of consecutive patients with COPD hospitalized at the Department of Respiratory Medicine between January 1990 and December 2015. We calculated for each patient the mean number of hospitalizations for AECOPD/year (H/y). We distinguished 2 groups (G) of patients. G1: <2 H/y and G2: ≥2 H/y. Predictors of multiple admissions identified by univariate analysis were included in the multivariate analysis. Results: The study included 1167 COPD patients (mean age 67 ± 10 years, 97% males). Three hundred six (26%) COPD patients had a mean number of hospitalizations per year ≥ 2. Multivariate logistic regression analysis demonstrated that an mMRC ≥ 2 (Odd ratio [OR] 1.8, 95% confidence interval [CI] 1.08 - 2.99, p = 0.022), a low PaO2 (PaO2 OR 0.97, 95% CI 0.95 - 0.99, p = 0.007) and frequent exacerbations (OR 2.95, 95% CI 2.56 - 3.39, p < 0.001) are independent factors associated with multiple admissions for AECOPD. Conclusions: An mMRC ≥ 2, a low PaO2 and frequent exacerbations are independently associated with multiple hospitalizations for AECOPD. The identification of these high risk COPD patients will be helpful in the decision of intervention strategies.