OBJECTIVES: Medication regimens with similar disease statuses may vary in complexity due to primary disease and/or other comorbidities. The aim of this study was to assess the medication regimen complexity score over one-year follow-up on primary disease and other comorbidities among moderate chronic obstructive pulmonary diseases (COPD) patients with earlier use of inhaled corticosteroids (ICS) or not. METHODS: A retrospective cohort study using the medication databases and electronic medical records obtained from China Medical University Hospital was conducted. Patients with moderate COPD were identified based on their lung function according to the 2009 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline. Selected patients were categorized into single therapy group (i.e., using long-acting bronchodilators [LAB] only) or combo therapy group (i.e., using LAB with ICS) based upon their respiratory medication use on the index date. Medication regimen complexity index (MRCI) scores for medications prescribed for COPD and other comorbidities were calculated and compared using descriptive and inferential analysis approaches on the index date and 360^thdate via the validated MRCI tool. RESULTS: Of 175 moderate COPD patients, 77 (44%) were in the combo therapy group. No significant differences of demographic and other comorbidities were observed between the combo and single therapy groups. On the index date and 360^th date, the combo therapy group had higher MRCI scores, especially for COPD-related medications (all p_s< 0.05). After one-year follow-up, the combo therapy group had incremental change of MRCI scores but the single therapy group had decremental change of MRCI scores on other comorbidities. CONCLUSIONS: Patients using combo therapy for their moderate COPD appeared to have different patterns of medication regimen complexity, particularly for COPD-related medication and the changes of other disease medications after one-year follow-up. Further research is warranted to evaluate the extent of contributing factors of MRCI score changes among moderate COPD patients.