To compare the outcomes of simple versus complicated femoral shaft fracture (FSF) treated by early intramedullary nail. Retrospective cohort study in level 1 trauma center including patients with FSF. Management consisted of intramedullary nailing (IMN) after adequate resuscitation within 24h. Data were prospectively collected on admission (trauma base) consisted of demographics, biological parameters, associated injuries and injury severity score (ISS). Complicated fractures consisted of type C fracture or any type associated with bilateral femur fracture, floating knee, associated femoral neck fracture, dislocated hip, concomitant neurovascular injury. Simple fractures were Isolated type A and B fracture. Simple and complicated fracture groups were compared using stratification by ISS (ISS < 16; 16 ≤ ISS < 25; ISS ≥ 25). Inclusion of 191 consecutive patients: simple FSF (N = 109) versus complicated FSF (N = 82) (type 32C, n = 36; bilateral, n = 44; associated neck of femur fracture, n = 15; floating knee, n = 36; concomitant femoral artery injury, n = 3 or sciatic nerve injury, n = 7). Complicated fractures were associated with higher rate of associated injuries (thoracic, 56.1 vs. 40.4%, p = 0.04; head 25.6 vs 10.1%, p = 0.005) and ARDS (12.2% vs. 3.7%, p = 0.046); longer ICU stay (12.8 vs. 7.3days, p = 0.019) and hospital stay (24.3 vs. 15.7days, p < 0.001). After stratification, differences in morbidity between simple and complicated FSF were significant solely in range 16≤ISS < 25. Complicated fractures had longer operation duration (297 vs. 151min, p < 0.001) due to additional IMN (tibial, humeral) requirements (24% vs. 1.8%, p < 0.001) and longer femoral IMN duration (133 vs. 104min, p < 0.05). Pseudarthrosis was higher in complicated fracture group (9.6 vs. 3.7%, p = 0.002). Complicated femoral fractures are associated with higher morbidity, especially in less severely injured polytrauma, which eventually results in longer hospital stay. Patients with moderate ISS and complicated fracture may have an increased risk of ARDS.