Background: Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of mortality worldwide and its prevalence among women increased in the past decade in developed countries mainly due to tobacco consumption and other risk factors. This study investigates sex-related differences of FEV1 decline in a real-life cohort. Methods: Prospective multi-centered study of COPD patients recruited between 2013 and 2022. Information collected at inclusion and visits: smoking status, symptoms, clinical characteristics, comorbidities. The evolution of FEV1 was analyzed in patients with 2 or more measures. Results: 3,228 patients were enrolled in the study. Women (36.5%) were younger, had lower BMI and were more current smokers than men patients (p<0.001). Regarding symptoms women had more dyspnea (p<0.009) and exacerbations (p<0.001). No sex differences were found for chest tightness and cough, except for more expectorations among men (p<0.004). For comorbidities men had more hypertension, ischemic heart disease, diabetes and less anxiety, depression, osteoporosis and asthma (p<0.001). Men had a lower predicted FEV1 (57.4%) than women (60.5%) (p<0.001) and a more severe COPD according to GOLD classification (p=0.005). No sex-related differences was observed for FEV1 decline. Conclusion: This study demonstrates differences on characteristics and some clinical aspects of women and men with COPD.Read less <