Background: The purpose of this study was to document outcomes following withdrawal of a single inhaler (step-down) in chronic obstructive pulmonary disease (COPD) patients on triple therapy (long-acting muscarinic antagonist and a combination of long-acting beta 2-agonists and inhaled corticosteroid), which a common treatment strategy in clinical practice.Methods: Through a retrospective observational study, COPD patients receiving triple therapy over 2 years (triple group; n=109) were compared with those who had undergone triple therapy for at least 1 year and subsequently, over 9 months, initiated inhaler withdrawal (step-down group, n=39). The index time was defined as the time of withdrawal in the step-down group and as 1 year after the start of triple therapy in the triple group.Results: Lung function at the index time was superior and the previous exacerbation frequency was lower in the step-down group than in the triple group. Step-down resulted in aggravating disease symptoms, a reduced overall quality of life, decreasing exercise performance, and accelerated forced expiratory volume in 1 second (FEV1) decline (54.7 +/- 15.7 mL/yr vs. 10.7 +/- 7.1 mL/yr, p=0.007), but there was no observed increase in the frequency of exacerbations.Conclusion: Withdrawal of a single inhaler during triple therapy in COPD patients should be conducted with caution as it may impair the exercise capacity and quality of life while accelerating FEV1 decline.