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We investigated the effects of primary (≤24 h) intramedullary femoral nailing on lung function and pulmonary hemodynamics in patients with multiple trauma. Two groups were separated: the group with primary femoral nailing with reaming (group RFN) was submitted to femoral nailing after reaming of the medullary canal; in the group with unreamed femoral nailing (group UFN) a small-diameter solid nail was inserted without reaming. Lung function was assessed by oxygenation ratio (Pao2/Fio2), and pulmonary hemodynamics by intraoperative pulmonary artery catheter measurements. Central venous blood concentrations of elastase and the platelet count were determined during and 3 days after surgery. Lung function was stable in UFN patients (n = 14), but deteriorated in RFN patients (n = 17) from 353 ± 24 (Pao2/Fio2 preoperatively) to 260 ± 28 (Pao2/Fio2 postoperatively) (p < 0.05) and improved only after 48 hours. Pulmonary artery pressure (PAP) did not change during surgery in UFN patients; in RFN patients PAP increased from 27.2 ± 3.1 mm Hg (preoperatively) to 36.3 ± 4.1 mm Hg (p < 0.05) upon reaming and normalized 1 hour after insertion of the nail. Femoral nailing after reaming represents a potential risk with respect to lung function disturbances. This might trigger the development of adult respiratory distress syndrome (ARDS), especially in patients at extra risk of this complication (additional lung contusion, “borderline patient”). In these cases unreamed femoral nailing might offer an alternative by allowing primary intramedullary stabilization without the risk of adverse effects to the lung.