Background: Infection has been associated with significant morbidity, mortality and increased medical cost after intramedullary nailing. The overall infection rate for open tibia fractures treated with the SIGN nail in LMICs was 11.9%. Prevalence of infection was observed to be high and was not investigated yet. Objective: To estimate the prevalence of infection and identify associated factors after intramedullary nailing of patients with open tibia fracture in Tibebe Ghion Specialized Hospital and Felege Hiwot Compressive Specialized Hospital from March 2020 to March 2022. Methods and Materials: A retrospective cross - sectional study design was employed on patients with open tibia fractures for whom intramedullary nailing was done in TGSH and FHCSH from March 2020 to March 2022. Patients with open tibia fractures treated with intramedullary nailing from March 2020 to March 2022 who fulfills inclusion criteria were included in the study and their charts and SIGN database were reviewed and analyzed. The data was entered ,coded ,cleaned on epi info version 7.1 and exported to SPSS and analyzed using SPSS windows version 23 software. . Descriptive statistics like frequency, mean, proportion were computed and displayed using tables and graphs. Binary logistic regression model was used to analyze the association between dependent and independent variables. Adjusted Odds ratio (AOR) and P-value < 0.05 was used to declare significant association. Result: The prevalence of infection was 15.04 %(95%CI 12.1 – 22.3). Among them 52.6% of patients were presented with pus drainage and only 30 % of patients required surgical debridement and irrigation and all most all patients were cured of infection. Gustilo – Anderson type (COR=4.894,95%CI:1.07-22.34), duration of surgery (AOR=5.488,95%CI:1.093 – 27.555) , associated injuries(AOR=6.175,95%CI:1.492 =25.567) and road traffic accident (AOR=21.509.95%CI:1.078 – 429.234) were highly associated with infection. Conclusion: The prevalence of infection was higher than some other studies. Even though the rate of over all infection is high , the rate of clinically significant infection that means infection treated by surgical debridement and irrigation is low. So it is safe to do primary nailing in open tibial fracture with acceptable level of infection. The rate of infection is highly associated with Gustilo –Anderson classification, presence of associated injury and the duration of surgery. Great attention should be given to multiple trauma patients. Every OR staff should also do procedures as quick as possible to decrease duration of surgery and we recommend further research by different method like prospective study to follow patients well.