OBJECTIVES: Medication complexity and comorbidities are common challenges among patients with chronic obstructive pulmonary disease (COPD). This study aimed to evaluate patterns and associated factors of medication regimen complexity index (MRCI) in COPD over one-year follow-up. METHODS: A retrospective cohort of adults aged ≥40 with GOLD Stage-2 COPD and using COPD-related medications in 2009 was identified. Demographic and clinical data for comorbidities was collected from electronic medical records. MRCIs and medication counts were calculated and compared at the index date, 90, 180, 270 and 360-day using multivariate analysis. RESULTS: On index date, Charlson Comorbidity index (CCI) score was 3.7±1.4 in 175 patients with moderate COPD. Diagnoses of dementia, renal disease and myocardial infarction were significantly correlated with increased non-COPD MRCI. Total medication count was 6.4±3.4, of which 2.0±0.1 were COPD-related, whereas the mean total MRCI score was 19.5±8.9 with COPD MRCI 8.3±0.3. Dosage form accounted for 48% of COPD MRCI and dosing frequency contributed to 68% of non-COPD MRCI. CCI was moderately associated with non-COPD MRCI at all time and total MRCI on index date, 90 and 180-day. During the one-year follow-up, COPD-related medication count significantly decreased. However, non-COPD and total medication counts increased and were strongly correlated, which were moderately associated with CCI. Correlation between total MRCI score and non-COPD MRCI was higher than that of COPD MRCI at all time. MRCI scores progressively decreased for COPD but increased for comorbidities during the first 270 days. Significant changes of MRCI scores were observed in COPD-related dosage form and dosing frequency, and comorbidity-related dosing frequency at 180 and 270-day. CONCLUSIONS: Close follow-up on medication regimen complexity patterns, for both COPD and comorbidities, is warranted to reduce medication burden in chronic COPD management. Further study includes impacts of MRCI on medication adherence and health outcomes, and interaction between COPD and comorbidity.