Background: Polypharmacy is the use of multiple medications, and it is common among elderly because of chronic diseases resulting in medication burden. Aim: to assess elderly patient's medication burden and their level of knowledge regarding Polypharmacy. Design: A descriptive research design was used. Setting: The study carried out at outpatients' clinics of Sohag university hospital that included (urology clinic, heart and chest clinic, internal medical clinic, neurology clinic and orthopedic clinic). Sample: Quota sample was used in this study,   Tools: three tools were used: Tool I: Interview questionnaire form included demographic and medical data, Tool II: Geriatric patient's knowledge questionnaire about poly pharmacy, and Tool III: Living with Medicines Questionnaire version 3.  Results: The results revealed that 54.3% of the studied elderly patients were < 70 years, majority of sample  were taking from 5-9 medications per day, about two thirds of them had poor knowledge regarding polypharmacy, highly statistical significant p value (p=0.000*) between knowledge score about polypharmacy and living with medications score. Conclusion: Elderly patients level of knowledge regarding polypharmacy and their medications were poor. In addition to, there was negative correlation and highly statistical significant between knowledge about polypharmacy, and medication burden. Recommendation: Designing health education programs for elderly and their families to increase knowledge regarding polypharmacy and  alleviate their medication burden.