To compare gender differences in the clinical expression of COPD patients attending a pulmonary clinic. We compared 53 FEV1-matched men and women with COPD attending a pulmonary clinic. We studied age, smoking pack-years history, Pao2, Paco2, functional residual capacity, body mass index (BMI), dyspnea, 6-min walk distance (6MWD), health-related quality of life, presence of comorbidities, and exacerbations in the previous year. Women were younger (57 years vs 65 years, p < 0.05), smoked less (48 pack-years vs 69 pack-years, p < 0.05), had better Pao2 (74 mm Hg vs 67 mm Hg, p < 0.05), lower Paco2 (40 mm Hg vs 45 mm Hg, p < 0.05), lower BMI (25 vs 28, p < 0.05), more exacerbations in the last year (1 vs 0, p < 0.05), and fewer comorbidities (Charlson score 2 vs score 4, p < 0.05) than men. Even though women had the same FEV1, better oxygenation, better Paco2, and fewer comorbidities, they performed poorer in walking distance (6MWD percentage of predicted, 87% vs 105%; p = 0.05), had worse quality-of-life scores (Saint George's Respiratory Questionnaire SGRQ symptoms score, 51 vs 41, p < 0.05; SGRQ activity score, 58 vs 47, p < 0.05), and had a higher degree of dyspnea (Modified Medical Research Council scale > 2, 28% vs 6%, p = 0.05). In a population of patients with COPD attending a pulmonary clinic, there are gender-related differences in the clinical expression of COPD that need further attention.