Introduction Assessing clinically important measures of disease progression is essential for evaluating therapeutic effects on disease stability in chronic obstructive pulmonary disease (COPD). This analysis assessed whether providing additional bronchodilation with the long-acting muscarinic antagonist umeclidinium (UMEC) to patients treated with inhaled corticosteroid (ICS)/long-acting β 2 -agonist (LABA) therapy would improve disease stability compared with ICS/LABA therapy alone. Methods This integrated post hoc analysis of four 12-week, randomized, double-blind trials (NCT01772134, NCT01772147, NCT01957163, NCT02119286) compared UMEC 62.5 µg with placebo added to open-label ICS/LABA in symptomatic patients with COPD (modified Medical Research Council dyspnea scale score ≥ 2). A clinically important deterioration (CID) was defined as: a decrease from baseline of ≥ 100 mL in trough forced expiratory volume in 1 s (FEV 1 ), an increase from baseline of ≥ 4 units in St George’s Respiratory Questionnaire (SGRQ) total score, or a moderate/severe exacerbation. Risk of a first CID was evaluated in the intent-to-treat (ITT) population and in patients stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) classification, exacerbation history and type of ICS/LABA therapy. Adverse events (AEs) were also assessed. Results Overall, 1637 patients included in the ITT population received UMEC + ICS/LABA ( n  = 819) or placebo + ICS/LABA ( n  = 818). Additional bronchodilation with UMEC reduced the risk of a first CID by 45–58% in the ITT population and all subgroups analyzed compared with placebo (all p  < 0.001). Improvements were observed in reducing FEV 1 (69% risk reduction; p  < 0.001) and exacerbation (47% risk reduction; p  = 0.004) events in the ITT population. No significant reduction in risk of a SGRQ CID was observed. AE incidence was similar between treatment groups. Conclusion Symptomatic patients with COPD receiving ICS/LABA experience frequent deteriorations. Additional bronchodilation with UMEC significantly reduced the risk of CID and provided greater short-term stability versus continued ICS/LABA therapy in these patients. Funding GlaxoSmithKline (study number: 202067). Plain Language Summary Plain language summary available for this article.