BACKGROUND: Factors influencing the decline in forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC) for chronic obstructive pulmonary disease (COPD) progression remain uncertain. We aimed to identify risk factors associated with rapid FEV₁/FVC decline in patients with COPD. METHODS: This multi-center observational study was conducted from January 2012 to December 2022. Eligible patients were monitored with symptoms, spirometric tests, and treatment patterns over 3 years. Rapid FEV₁/FVC decliners were defined as the quartile of patients exhibiting the highest annualized percentage decline in FEV₁/FVC. RESULTS: Among 1,725 patients, 435 exhibited rapid FEV₁/FVC decline, with an annual change of -2.5%p (interquartile range, -3.5 to -2.0). Rapid FEV₁/FVC decliners exhibited lower body mass index (BMI), higher smoking rates, elevated post-bronchodilator (BD) FEV₁, higher post-BD FEV₁/FVC, and a lower prevalence of Staging of Airflow Obstruction by Ratio (STAR) stage IV. Rapid FEV₁/FVC decline was not linked to the annual exacerbation rate, but there was an association with symptom deterioration and FEV₁ decline. In multivariable analyses, low BMI, current smoking, increased modified Medical Research Council dyspnoea score, low post-BD FEV₁, low STAR stage, high forced mid-expiratory flow (FEF CONCLUSION: We identified the risk factors for rapid FEV₁/FVC decline, including BMI, smoking, symptoms deterioration, FEV₁ decline, and adherence to standard inhaler treatment. Our findings underscore the potential benefits of maintaining consistent use of long-acting beta-agonist/long-acting muscarinic antagonist even in the presence of worsening symptoms, in attenuating FEV₁/FVC decline.