Background: Intramedullary nailing is the treatment of choice for the majority of tibial shaft fractures and anterior knee pain is the most common complication of this surgery; however, its etiology is still unknown. The purpose of this study was to assess the predicting factors related to anterior knee pain following tibial nailing. Materials and Methods: Patients with isolated, unilateral tibial shaft fracture who had undergone tibial nailing were identified retrospectively. Data including age, sex, type of fracture, technique of surgery and location of the nail were collected and finally the association between the above variables and knee pain were analyzed via SPSS software. Results: A total of 95 patients participated in the study. The mean age of the participants was 33.52 ± 1.62, 87 (91.6%) of whom were male and 74 (77.9%) had close fractures respectively. The method of surgery in 60 (63.2%) patients was paratendinous approach and in 35 (36.8%) was transtendinous. Twenty six (27.4%) of the patients had anterior knee pain. There were no significant differences between the two groups of patients with and without knee pain by age, sex, type of fracture and type of surgery (P = 0.952, 0.502, 0.212 and 0.745, respectively). Patients with protrusion of the nail from the anterior cortex had higher risk of developing knee pain after surgery (odds ratio: 2.76, confidence interval: 1.08, 7.08, P = 0.031). Conclusion: The results revealed a higher risk of developing anterior knee pain after tibial nailing in patients with protrusion of the nail from the anterior cortex.