Polypharmacy especially in elderly is a challenging public health problem all over the world that leads to increased hospitalization, poor quality of life and represents an economic burden. Aim: The current study aimed to assess knowledge, associated factors, and adverse outcomes 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. Four tools were used in the present study; A structured interview questionnaire, Elderly's knowledge of polypharmacy interview questionnaire, Associated factors of polypharmacy interview questionnaire, and Polypharmacy adverse outcomes interview questionnaire. Results: The present study results revealed that the studied elderly patient's age ranged between 60 and 75 years, with mean 66.29 ±3.904, 32.5 % don’t read or write, 98% were having chronic diseases, 92% of the studied elderly had poor scores of knowledges regarding polypharmacy, 77.5% had high polypharmacy associated factors, and 63% had high polypharmacy adverse outcomes. Conclusion: A statistically significant negative correlation was found between polypharmacy knowledge and associated factors, and between knowledge and adverse outcomes. On the other hand, there was a statistically significant positive correlation between polypharmacy associated factors and adverse outcomes. Recommendations: Development of educational programs to raise the older adult's awareness and familiarity of their medications to gain appositive health outcomes with minimal number of medications.