On-site sanitation systems have been used on a large scale and widely used in both developing and developed countries, whereas used the areas with no sewerage facilities. On-site sanitation includes excreta and wastewater which are collected, stored, and treated when they are generated; the objective of this study was to assess the sustainability of on-site sanitation system from user interfaces to disposal, in the case of Debre Birhan town. To meet the objective, a milt-criteria approach, which comprised of economical, socio-cultural, environmental, health, and technical function, was applied. The required data were collected through questionnaires, focus group discussions, and key informant interviews. Accordingly, a survey of 379 households, 10 focus group discussions and five key informative interviews were conducted in four sub-cities. The research formulated risk assessment matrix to identify the factors that are related to the sustainability of on-site sanitation system in Deber Birhan town by giving score and color coding from one to five (1-5) with one for poor performance and five for very good performance and red color for low result and blue color for very good result performance. The results of the research showed that the onsite sanitation in Deber Birhan is not properly managed. According to the research, many people are attacked by Diarrhea and cholera, which is because the onsite sanitation is not safe. The most dominant onsite sanitation technology in all the considered sub-cities is simple pit latrine. The shift flow diagram (SFD) shows that only 13% of fecal sludge is safely managed. Thus, it is required to work on improving the existing sanitation system so that risk of illness is reduced and to increase overall community resilience. Key words: Debre Birhan, on-site, pit latrine, sanitation system, sustainability