Objective To analyze the current situation of medication discrepancy in elderly patients taking multiple drugs during the hospital-to-home transitional period, and explore the correlation between medication discrepancy and discharge guidance and readiness for hospital discharge. Methods A total of 265 elderly patients taking multiple drugs were selected and investigated using a general information questionnaire, the Quality of Discharge Teaching Scale (QDTS), Readiness for Hospital Discharge Scale (RHDS) on the day of discharge.One week after discharge, the medication discrepancy tool (MDT) was used for telephone follow-up of patients. Results The incidence of medication discrepancy within 1 week after discharge was 61.89%. The main type of and reason for discrepancy was the decrease in the types of medication (40.28%), and patient-originated (53.61%) respectively. Medication discrepancy was negatively correlated with the quality of discharge teaching and readiness for discharge (both P<0.05). The results of regression analysis showed that age, residence condition, medications prescribed at discharg, length of stay, number of diseases and quality of discharge teaching were the influencing factors of medication discrepancy (all P<0.05). Conclusion The incidence of medication discrepancy is high among elderly patients with multiple drugs in hospital-to-home transitional period for many reasons. Therefore, medical staff should streng the nthemanagement for medication discrepancy, and improve quality of health guidance at discharge, so as to ensure medication safety.