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To investigate the success of exchange reamed femoral nailing in the treatment of femoral nonunion after intramedullary (IM) nailing, and to analyze factors that may contribute to failure of exchange reamed femoral nailing.Retrospective consecutive clinical series.Level I trauma center and tertiary university hospital.Twenty-three patients were identified whose radiographs failed to show progression of healing for four months after treatment with a reamed IM femoral nail. Nineteen patients had undergone primary IM nailing of an acute femoral shaft fracture, one patient had been converted to an IM nail after initially being treated in an external fixator, and three patients had previously undergone an unsuccessful exchange reamed nailing.All patients were treated by exchange reamed femoral nailing. The diameter of the new nail was one to three millimeters larger than that of the previous nail (the majority were two millimeters larger). The intramedullary canal was over-reamed by one millimeter more than the diameter of the nail. Most of the nails were statically locked, and care was taken to avoid distraction of the nonunion site by reverse impaction after distal interlocking was performed or by applying compression with a femoral distractor.Radiographic evaluation of union was determined by the presence of healing on at least three of four cortices. Factors reviewed included the patient's age, smoking history, mechanism of injury, associated injuries, whether the initial fracture was open or closed, the pattern and location of the fracture, the type of nonunion, the increase in nail diameter, whether the nail was dynamically or statically locked, and the results of any intraoperative cultures.Tobacco use was found to have a detrimental impact on the success of exchange reamed nailing. All eight of the non-smokers healed after exchange reamed nailing, whereas only ten of the fifteen smokers (66.7 percent) healed after exchange reamed nailing. Overall, exchange reamed femoral nailing was successful in eighteen cases (78.3 percent). Three patients achieved union with additional procedures. Intramedullary cultures were positive in five cases; all of these achieved successful union.Exchange reamed nailing remains the treatment of choice for most femoral diaphyseal nonunions. Exchange reamed IM nailing has low morbidity, may obviate the need for additional bone grafting, and allows full weight-bearing and active rehabilitation. Tobacco use appears to have an adverse effect on nonunion healing after exchange reamed femoral nailing.