Abstract Introduction-in Ethiopia, information on fracture-related infection among patients with femoral fractures is limited, particularly regarding factors that may influence its occurrence. This lack of local evidence makes it difficult to fully understand the problem and to plan effective prevention measures. Therefore, this study was conducted to identify factors associated with fracture-related infection among patients treated for femoral fractures at TibebeGhion Specialized Hospital Objective-To assess determinants of fracture-related infection following internal fixation of femoral fractures Methodology-A case–control study was conducted at TibebeGhion Specialized Hospital, Bahir Dar, Ethiopia, using medical records from August 2022 to September 2025. A total of 128 participants (64 cases and 64 controls) were included, with controls selected systematically. Data were analyzed using SPSS version 27. Bivariable and multivariable logistic regression analyses were performed to identify factors associated with fracture-related infection. Model fitness was assessed using the Hosmer–Lemeshow goodness-of-fit test and a p-value of <0.05 was considered statistically significant. Result-The mean age of patients with fracture-related infection was 27.47 ± 8.44 years, and males accounted for 89.8% of the study population.After adjusting for potential confounders in the multivariable logistic regression analysis, delayed debridement beyond 24 hours remained independently associated with fracture-related infection (AOR = 5.30; 95% CI: 1.19–23.81; p = 0.028). Likewise, patients whose wounds were closed after 72 hours had nearly seven times higher odds of developing infection compared to those who received early wound closure (AOR = 6.97; 95% CI: 1.71–28.49; p = 0.007). Prolonged duration of surgery exceeding two hours also remained a significant predictor of fracture-related infection (AOR = 5.14; 95% CI: 1.09–24.14; p = 0.038). Conclusion- Fracture-related infection among patients with femur fractures was independently associated with delayed debridement, delayed wound closure, and prolonged operative time.