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Compared to the last two decades, an increase in chronic obstructive pulmonary disease (COPD) prevalence, morbidity, mortality and disability has clearly emerged among women both in Europe and in all other countries. Despite this evidence, in the international guidelines for COPD there are no sex-specific recommendations. The aim of this study is to evaluate gender differences in patients hospitalized for COPD in Puglia (Italy), with regard to number of admissions, mean age, average length of stay in hospital (ALOS), hospital mortality, re-hospitalization and presence of comorbidities. To identify COPD hospitalized patients, we relied on the Puglia Hospital Discharge Register Database. We included all patients discharged with principal diagnosis of COPD with or without exacerbation (respectively ICD-9-CM codes 491.21 and 491.20) between 2005 and 2016. There has been an increase in the proportion of women’s hospitalizations for COPD, from 2005 [31.9%, 95% confidence interval (CI) 31.1-32.7] to 2016 (37.9%, 95%CI 36.0-40.0). Women need longer hospitalization and in 2016 the proportion of women’s re-hospitalization was greater compared to men. Despite these data, women are less treated with respiratory therapy (ICD-9- CM 93.9x) than men in all the examined years and wards. The prevalence of most common comorbidities is higher among women. The number of COPD hospitalized patients had been reduced in Puglia between 2005 and 2016, with an important increase of female COPD patients, female average age, ALOS and re-hospitalization. Women are treated less and have more comorbidities with a negative impact on clinical progression of COPD, survival and quality of life.