The authors investigated the prevalence and the difference in the severity of systemic complications following intramedullary nailing of bilateral tibial and femoral shaft fractures. A retrospective chart analysis of 12 consecutive patients with bilateral tibial shaft fractures (TF) and 14 patients with bilateral femoral shaft fractures (FF) was performed. The incidences of bilateral tibial fractures and bilateral femoral shaft fractures were 3.8% and 4.6% respectively. The median Injury Severity Score (ISS) in TF group was 13 (9-29) compared to 16 (9-34) in the FF group (p = 0.169). The mean resuscitation requirements were 4.2 (3-11) litres of colloids and crystalloids and 1.7 (0-10) units of blood in the TF group and 10.6 (6-16) litres of colloids and crystalloids and 9.2 (5-25) units of blood in the FF group (p = 0.002). In the TF group there was 1 death compared to 2 in the FF group. In the TF group, there were 2 cases of ARDS, 4 cases of deep sepsis and 3 above knee amputations. In the FF group, there were 6 cases of ARDS (p = 0.04), 1 case of deep sepsis and 1 above knee amputation. Patients with bilateral tibial shaft fractures revealed lower ISS, resuscitation requirements, ARDS, associated injuries, and mortality when compared to bilateral femoral shaft fractures. This is probably due to the anatomical difference in the morphology of the bones, volume of liberated intravascular marrow fat, organisation and layout of the venous capillary network and severity of associated injuries.