Background The use of retrograde nailing for gunshot wound femur fractures is controversial due to concerns of knee sepsis after this procedure since the knee is entered to introduce the nail into the canal. Questions/purposes We compared retrograde and antegrade nailing for gunshot femur fractures to determine whether (1) knee sepsis or other adverse events were more likely to complicate procedures using retrograde nails, (2) there were differences in surgical time or blood loss, and (3) there were differences in radiographic union.Methods We retrospectively reviewed our prospective trauma database from 1999 to 2012 for patients with a diagnosis of gunshot and femur fracture. We performed a detailed review of medical records and radiographs for those patients with OTA Classification Type 32 femur fractures secondary to gunshot injury treated with either retrograde or antegrade femoral nailing. Eighty-one patients were treated with intramedullary nailing (53 retrograde and 28 antegrade). We reviewed elements of the operative treatment (procedure, anesthesia time, operative time, and estimated blood loss) for all 81 patients. For clinical and radiographic review, followup was adequate for 43 and 25 patients with retrograde and antegrade nailing, respectively. Minimum followup was 3 months for both groups (retrograde: mean, 41 months; range, 3-148 months; antegrade: 26 months: range, 3-112 months). Results No patients in either group developed knee sepsis. No significant differences were found between groups with regard to operative time, blood loss, or radiographic union. Conclusions With the numbers available, immediate retrograde nailing appears as safe and effective as antegrade nailing for gunshot femur fractures. Immediate retrograde nailing is as safe as antegrade nailing for gunshot femur fractures. Level of Evidence Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.