Objective: To investigate the effect of systematic pharmaceutical intervention by clinical pharmacists on potentially inappropriate medication (PIM) in elderly hospitalized patients with polypharmacy, and to provide realworld evidence for establishing standardized medication management models and preventing medicationrelated risks in the elderly population. Methods: A total of 246 elderly inpatients with polypharmacy admitted to the Department of Respiratory and Critical Care Medicine of the hospital from January 2024 to June 2025 were enrolled. They were divided into a control group and an observation group according to the order of admission, with 123 cases in each group. The control group received routine diagnosis and treatment plus basic medication instructions; the observation group received integrated pharmaceutical interventions on the basis of routine care, including medication reconciliation upon admission, dynamic medication order review, individualized medication education, and discharge medication counseling. The incidence of PIM, the average number of PIM items per patient, and the incidence of moderatetosevere drugdrug interactions were compared between the two groups at admission and discharge. Adverse drug reactions during hospitalization and the acceptance rate of pharmacists’ recommendations were also recorded. Results: There was no statistically significant difference in baseline characteristics between the two groups (P > 0.05). At discharge, the number of patients with PIM and the average number of PIM items per patient in the observation group were significantly lower than those in the control group (both P < 0.001). The incidence of drugdrug interactions at discharge and the incidence of adverse drug reactions during hospitalization in the observation group were also significantly lower than those in the control group (both P < 0.01). During the intervention period, clinical pharmacists proposed 216 medication optimization recommendations, of which 179 were accepted by physicians, yielding an acceptance rate of 82.87%. Conclusion: Comprehensive systematic pharmaceutical intervention can effectively reduce the number of PIM items in elderly inpatients with polypharmacy, lower the risk of adverse drug interactions and adverse drug reactions, and promote continuous optimization of multidrug regimens in elderly patients. This physicianpharmacist collaborative model is worthy of promotion in general internal medicine wards for the elderly.