Summary Study objectives To determine the medications prescribed to patients with chronic obstructive pulmonary disease (COPD) and their relationship to health-related quality of life (HRQL). Methods Cross-sectional study of 611 consecutive patients with stable, mild-to-severe COPD who attended at the respiratory service of a single hospital during a 1-year period. HRQL was evaluated using the St. George Respiratory Questionnaire (SGRQ) and the Short Form 36-item (SF-36) questionnaires. Linear regression analysis was used to determine the influence of the number or type of medication on the total SGRQ score, adjusting by disease severity and other relevant variables. Results Significant differences were observed among the number of drugs prescribed according to dyspnea levels, percentage of predicted FEV 1 (FEV 1%), SGRQ scores and some areas of SF-36. Fifty-nine percent of patients with an FEV 1%>50% were prescribed inhaled corticosteroids (ICS). Those who took an ICS had a worse HRQL than patients with an FEV 1%>50% who did not receive ICS. Conclusions A relationship exists between the number of medicines prescribed to patients with COPD and their HRQL, measured by the total SGRQ score, after adjustment by severity of the disease. Within the group of patients who should not have been prescribed ICS, there are subgroups that might benefit from this medication.