Objective: To investigate the main reasons of drug return in our hospital, put forward relevant countermeasures to promote rational clinical medication. Methods The drug return data were collected and processed with Excel software. The Pareto diagram analysis was used to analyze the main reasons of drug return. Results: The main reasons leading to drug return were adverse drug reactions, drug irrational use, condition changes, and patients. The secondary reasons were hospitalization after initial outpatient therapy or hospital transfer and cancellation of the medical exam, and the rest reasons were summed up as general factors. Conclusion: According to the main reasons of drug return, a series of measures including strengthening system construction and prescription evaluation, improving doctor’s diagnosis ability and service consciousness, enhancing pharmacist’s professional competence should be taken to limit the primary and secondary factors into the controllable and acceptable range.