Background: Polypharmacy poses a growing challenge to healthcare systems because of its association with adverse effects and the misuse of medication. This study aimed to identify the sociodemographic factors and comorbidities associated with polypharmacy.Methods: We selected patients aged ≥30 years registered in the National Health Information Database in 2018 who were prescribed at least one medication for ≥180 days. Multivariate logistic regression analyses were performed to evaluate the associations between polypharmacy, sociodemographic characteristics, and comorbidities.Results: Polypharmacy was significantly associated with increasing age, with the strongest association observed in adults aged ≥65 years. Compared with medical aid recipients, higher-income groups had a weaker association with polypharmacy. After adjusting for covariates, significant associations with polypharmacy were found for specific comorbidities, such as Parkinson disease (odds ratio [OR], 3.804; 95% confidence interval [CI], 3.733–3.876; P<0.001) and chronic ischemic heart disease (OR, 3.199; 95% CI, 3.178–3.221; P<0.001).Conclusion: These findings may help reduce the burden of polypharmacy by facilitating the development of targeted strategies tailored to patients.