BACKGROUND: Worldwide, the supply of organs continues to be much less than the demand. Many studies identify poor knowledge and negative attitude about organ donation for this. The purpose of this study was to assess knowledge and attitude towards organ donation and associated factors among people who accompany patient during hospital visit at tertiary hospital in Ethiopia.METHODS: A hospital-based cross-sectional study was conducted from March 1st to May 31, 2019, at a tertiary hospital and the only transplant center in Ethiopia. The patient companions were interviewed with structured questionnaires. Descriptive statistics were presented and factors associated with good knowledge and favorable attitude were assessed using Binary logistic regression.RESULTS: A total of 414 patient companion participated in the study. The mean age of the respondents was 35+13years, and 252(60.9%) were males. Forty-four (10.6%) of the study participants had good knowledge about organ donation. Male gender was significantly associated with improved knowledge (AOR=2.127 95% CI: 1.036, 4.368). A favorable attitude towards donation was found in 219(52.9%) of the study participants. Participants who had completed secondary education were more likely to have unfavorable attitude towards organ donation (AOR=0.498, 95% CI: 0.290, 0.857).CONCLUSION: Knowledge about organ donation was found to be poor, and attitudes towards organ donation were found to be unfavorable among patient companions at a major medical center in Ethiopia. Strategies focused on education of the general public and broad dissemination of information on the benefits of organ donation will be critical for improving the organ donor pool.