Background:- The peak incidence of Human Immunodeficiency Virus (HIV) infection occurs among adults who are at the most productive age of the population. They are vulnerable to HIV because of their age, living arrangement, and cultural influences. Objective:- The aim of this study is to determine the prevalence of HIV infection and its risk factors among adults in Negele Borena Hospital. Method:- A cross-sectional study was conducted on 384 adults in Nagele Borena Hospital from April to September, 2017. Self-administered questionnaire was used to collect data on socio-demographic variables, knowledge of HIV/STIs and behavioral factors. In collaboration with the hospital work, whole blood samples were tested for the presence of antibody to HIV infection using National HIV rapid diagnostic tests algorithm. Chi-square test was conducted to identify risk factors, and finally, regression analysis was computed to identify the independent risk factors that influence the incidence of HIV/AIDS. Results:- The sero-prevalence of HIV was 11(2.86%) where 4(2.03%) and 7(3.74%) were males and females respectively. Alcohol drinking (AOR=5.2(1.1-25) and khat chewing (AOR=5.8, 95%CI 5.8 (1.3-27) discuss about sexual issues openly with their family AOR=13, 95%CI 13(1.6-102), peer pressure AOR=22.9, 95%CI22.9 (3.9-131) and multiple sexual partner (AOR=5.2, 95%CI 5.2(0.9-29) were the risk factors for HIV infection and HIV/AIDS transmission determinants. Conclusion and recommendation:- The prevalence of HIV infection among adults of Negele Borena Hospital is high. New infection among young people suggested that the disease is not under control yet in the country. Therefore, planning strategy to prevent the spread of HIV infection in town is critical. Keywords: Behavior, HIV/AIDS, prevalence, risk factor, transmission DOI : 10.7176/JHMN/68-03 Publication date: November 30 th 2019