Objective. To identify and explain differences between men and women with asthma regarding health-related quality of life (HRQoL). Methods. A cross-sectional study was performed among 967 asthma patients recruited from general practice. Data were collected by means of a pulmonary function assessment, a face-to-face interview, and a written questionnaire. Results. Women with asthma reported lower scores on HRQoL in the age groups 16-34 and 56-75 years but not in the age group 35-55 years. In all age groups, women reported more severe dyspnea but had higher levels of pulmonary function. The poorer HRQoL reported by women could be explained by a more severe dyspnea and a higher level of medication use in women. Conclusions. The finding that women with asthma aged 16-34 and 56-75 years report poorer HRQoL than men is not due to a more severe disease state in terms of pulmonary obstruction but does seem to be related to a more severe subjective disease state in women than in men.