Background: Oder adults are more prone to polypharmacy that much more complex than just the number of medications. polypharmacy leads to increased hospitalization, poor quality of life and represents an economic burden especially in developing countries like Egypt. Aim: The present study aimed to assess knowledge and associated factors of polypharmacy among elderly patients. Design: A descriptive design was utilized to conduct the present study. Setting: The study was conducted at the outpatient clinics at Zagazig University Hospitals. Sample: A purposive sample composed of 200 elderly patients. Tools: three tools were used in the present study. Tool I: A structured interview questionnaire. Tool II: Elderly's knowledge of polypharmacy interview questionnaire. Tool III: Associated factors of polypharmacy interview questionnaire. Results: the present study results revealed that 92% of the studied elderly had poor score of knowledge about polypharmacy and 77.5% of the studied elderly had high score of polypharmacy associated factors. Conclusion: There was a statistically significant negative correlation between polypharmacy knowledge and associated factors. Recommendations: Development of Educational programs to raise the older adult's awareness and familiarity of their medication to gain appositive health outcomes with minimally number of medications.