OBJECTIVE: The purpose of this study was to determine the incidence of deep venous thrombosis (DVT) in a prospective protocol of early spanning external fixation with the concurrent use of low-molecular weight heparin (LMWH) in patients with high-energy lower extremity trauma. SETTING: Three level I trauma centers. DESIGN: Prospective observational study. PATIENTS: One hundred thirty-six consecutive patients with 151 complex lower extremity injuries were treated with a protocol of immediate joint spanning external fixation application and LMWH administration within 24 hours of admission. A total of 143 external fixators were applied. Early patient mobilization was encouraged and possible due to the skeletal stability provided by the external fixator. There were 87 men and 49 women with a mean age of 43 years. There were 62 proximal tibia fractures (Orthopaedic Trauma Association [OTA] Fracture Classification 41), 4 tibial shaft fractures (OTA 42), 49 distal tibia-fibula fractures (OTA 43, 44), 14 femur fractures (OTA 32, 33), 8 calcaneus fractures (OTA 73), 10 knee dislocations, and 4 talus fracture dislocations. Forty-eight injuries (32%) were open. INTERVENTION: Temporary joint spanning external fixator placement, LMWH administration, and early mobilization within 24 hours of admission. Duplex ultrasonography of the bilateral lower extremities within 1 day to 3 days before fixator removal and definitive fixation procedure. MAIN OUTCOME MEASUREMENTS: Presence of DVT on duplex ultrasound examination. RESULTS: Duplex ultrasonography was negative for DVT in all but three patients for an incidence of 2.1% (3 of 143 fixators). There were no bleeding complications secondary to the use of LMWH while the temporary external fixator was in place. CONCLUSION: The incidence of DVT in patients treated with a protocol of early joint spanning external fixation and LMWH administration does not exceed historical controls. The early restoration of limb length, alignment, and stability allows early mobilization, which may contribute to the prevention of DVT.