OBJECTIVE: This study aimed to determine the prevalence of polypharmacy, comorbidities and to investigate factors associated with polypharmacy among adult patients with Chronic Obstructive Pulmonary Disease (COPD). METHODS: This was a retrospective single-centre cross-sectional study. Patients with a confirmed diagnosis of COPD according to the GOLD guidelines between 28 February 2020 and 1 March 2023 were included in this study. Patients were excluded if a pre-emptive diagnosis of COPD was made clinically without spirometry evidence of fixed airflow limitation. Population characteristics were presented as frequency for categorical variable. Logistic regression analysis was used to identify predictors of polypharmacy. RESULTS: The study sample included a total of 705 patients with COPD. Most of the study sample were males (60%). The mean age of the study population was 65 years old. The majority of the study population had comorbid diseases (68%), hypertension and diabetes were the most common co-existent diseases. Around 55% of the study sample had polypharmacy. Females were significantly less likely to be on polypharmacy compared to males (OR = 0.68, 95% CI = [0.50-0.92], P-value = 0.012)). On the other hand, older patients aged 65.4 or more (OR = 2.31, 95% CI = [1.71-3.14], P-value ≤ 0.001), those with high BMI (≥ 29.2) (OR = 1.42, 95% CI = [1.05-1.92], P-value = 0.024), current smokers (OR = 1.9, 95% CI = [1.39-2.62], P-value ≤ 0.001), those who are receiving home care (OR = 5.29, 95% CI = [2.46-11.37], P-value ≤ 0.001), those who have comorbidities (OR = 19.74, 95% CI = [12.70-30.68], P-value ≤ 0.001) were significantly more likely to be on polypharmacy (p ≤ 0.05). CONCLUSIONS: Polypharmacy is common among patients with COPD. Patients with high BMI, previous ICU hospitalization and older age are more likely to have polypharmacy. Future analytical studies are warranted to investigate outcomes in patients with COPD and polypharmacy.