Background: There is limited evidence on nurses’ knowledge and perceived barriers to prevent pressure ulcer in Ethiopia. The present study aimed to assess nurses’ knowledge and perceived barriers to prevent pressure ulcer in public hospitals in Addis Ababa, Ethiopia. Methodology: A self-reported cross-sectional survey design was used to collect data from 356 nurses who were providing care to patients with pressure ulcers between 21 April and 28 May 2015. We used a structured questionnaire, which was adapted from previous studies to collect the data. Data were coded and entered in computer using EPI data version 3.1 statistical packages, and transported into SPSS version 20 for data analysis. Descriptive statistics were used to describe demographic characteristics, level of nurses' knowledge on PU prevention and treatment, and perceived barriers to carry out PU prevention and treatment. Results: Findings of the present study revealed that the majority of nurses who participated in this study had unsatisfactory knowledge (63.85%) as regards the pressure ulcers management. Nurses were questioned to specify their agreement about the presence of specific barriers in the work environment. Shortage of staff was the utmost frequently cited barrier to carrying out PU-prevention measures (83.1%), followed by limited resources (67.7%) and lack of guidelines (policies) about PU prevention (59.8%). Conclusions: In-service training and educational program should be designed for nurses to enhance their Knowledge and practice. Satisfactory dissemination of PU prevention and treatment guidelines appears to be essential to advance quality of PU prevention and treatment.