Purpose: In patients following severe trauma sometimes the physiological condition or soft tissue status may not allow definitive fixation of a femoral fracture. In these patients, an external fixator can be placed to temporarily stabilise the fracture, after which definitive fixation can be performed in a second procedure. The aim of this study was to compare the postoperative wound infection and union rates of patients treated with direct intramedullary nailing (IMN) and patients treated with the ‘two-stage treatment’. Methods: All patients with high-energy femoral fractures treated with IMN between 2000 and 2016 in a single Level 1 trauma centre were eligible. Electronic charts were reviewed for patient and surgical characteristics; furthermore, the development of complications was noted. A propensity score analysis was performed to assess the attributed risk of the external fixator on the development of postoperative wound infections. Results: A total of 149 patients were included in this study; 93 underwent direct IMN and 56 underwent the two-stage treatment. Patients who underwent two-stage treatment were more severely injured, reflected by lower EMV and higher ISS on admission. Patients in the two-stage treatment group had a significant higher risk of postoperative wound infections (OR: 4.698, 95% CI: 1.203–18.339) but not a higher risk on deep postoperative wound infections (OR 2.345, 95% CI: 0.439–12.540). Union rate did not differ between the two groups (94% vs 94% NS). Conclusions: The two-stage treatment is a safe treatment option in patients with a high-energy femoral fracture in terms of postoperative wound infections. Union rates are also comparable between the two treatment groups.