BACKGROUND: Infections has been associated with significant morbidity, mortality and increased medical cost after SIGN nailing. It complicates up to 1-3% closed and 10 % of open fractures, which can rise up to 50% in severe forms. long bone fractures are one of the most common limb fractures representing a significant portion of the trauma workload. Most of them need surgical treatment, including SIGN nail which is widely accepted and practiced in Ethiopia. OBJECTIVE: To estimate the incidence and to identify factors associated with surgical site infection after intramedullary SIGN nailing of long bone fractures in patients operated with a SIGN nail in TGSH. METHODS AND MATERIALS: The study was conducted using a retrospective cross-sectional study in patients who were admitted and operated with SIGN nail from January 2018 to September 30/2020 who fulfill the inclusion criteria. Cases with SIGN nail were reviewed and cases with SSI were analyzed in particular. The data was entered and analyzed using SPSS windows version 23 software. Descriptive statistics like frequency tables and descriptive summaries were used to describe the variables. Binary logistic regression model was used to analyze the association between variables. Bi variable and multivariable logistic regression analysis were used and the results were presented in tables and charts. Odds ratio (OR) was used to compare associations between dependent and independent variables. Results: The overall incidence of infection was 5.2 %. It varies with the nature and severity of injury which is 10.7% in open fractures and 1.7% in closed fractures. In open injuries infection rate increases as severity increases accounting 1.33%,2.67% and 10.67% for grade I, grade II and grade IIIA fractures respectively. Conclusion and Recommendation The present study showed overall incidence of infection is comparable to LMICs but higher than developed countries. Complex, open fractures whose surgeries were done early and external fixator use were found to be associated factors for infection. So, more attention should be given to patients with long bone fractures on SIGN nails for complaints around the surgical wound and we recommend further study on this topic. Keywords: long bone fracture, associated factor, SIGN, surgical site infection.