Background site infection (SSI) is disastrous in orthopedic practice as it is difficult to rid the bone and joint of the infection. Despite being a preventable complication of surgical procedures, surgical site infections (SSIs) continue to threaten public health with significant impacts on the patients and the health-care human and financial resources and it was expected to Surgical had similar impact in the Tibebegion specialized hospital. This study was aimed to assess prevalence and associated factors with surgical site infection after intramedullary nailing with surgical implant generation network (SIGN) of open femur fracture. The number of patient with open femur fracture in the TGSH in the past two years were increased due to the war that happen in the northern part of Ethiopia, but there was no study done on the above title . Methods A cross sectional study design was used to conduct the study on All patients admitted with a diagnosis of open femur fracture and operated with SIGN nails in the orthopedic and trauma surgery department at TGSH from January 1/2020 to July 1/2023 G.C fulfilling the inclusion criteria were included in study group. The data which were collected from on the chart from hospital records and obtained from electronic data from SIGN online surgical database. Analyses were made by Binary logistic regression to find out the association between infection and associated factors. The strength of association was estimated using AOR with 95% confidence interval and P <0.05. Result A total of 115 of 125 patients (92.0%) were included: 100 males and 15 females with the mean age of 29.83 +-10.105 years. The estimated prevalence of SSI was 12.2% .Results of Binary logistic regression showed that timing of starting antibiotics from injury (AOR =3.981; 95%CI 1.035-15.317) and number of debridement before definitive surgery (AOR = 3.915; 95%CI 1.093-14.023) was significantly associated with SSI. Conclusion .The magnitude of Surgical site infection was lower in the study area:, That might be due to increased experience of orthopedic team in TGSH by managing patient with open fracture due to more patient exposure .Delayed timing of starting antibiotics more than 6 hour and more than one debridement before definitive surgery were statistically associated with surgical site infection. Key words: Femur fracture, intramedullary nail, Open fracture, surgical site infection