Background: Polypharmacy, particularly in the elderly, is a formidable global public health problem that increases hospitalization, lowers quality of life, and represents an economic burden. Aim of the study: Assess knowledge, associated factors, and adverse outcomes of polypharmacy among elderly patients. Subjects and Methods; Design: A descriptive design was utilized. Setting: The study was carried out at Zagazig University Hospitals' outpatient clinics. Subjects: Purposive sample composed of 200 elderly patients. Tools of data collection: Tool I: A structured interview questionnaire. Tool II: Elderly's knowledge of polypharmacy interview questionnaire. Tool III: Associated factors of polypharmacy interview questionnaire. Tool IV: Polypharmacy Adverse outcomes interview questionnaire. Results: 92% of the studied elderly had poor score of knowledge regarding polypharmacy, 77.5% had high associated factors, and 63% had high adverse outcomes. Conclusion: A statistically significant negative correlation was found between polypharmacy knowledge and associated factors, and between knowledge and adverse outcomes. Conversely, there was a statistically significant positive correlation between polypharmacy associated factors and adverse outcomes. Recommendation: Designing educational programs to increase medication awareness and familiarity among older adults, to improve health outcomes with fewer prescriptions needed.