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The current “gold standard” for treatment of chronic fracture nonunion in the metaphyseal-diaphyseal region of the fifth metatarsal is intramedullary screw fixation. Complications with this procedure, however, are not uncommon. Shock wave therapy can be an effective treatment for fracture nonunions. The purpose of this study was to evaluate the safety and efficacy of shock wave therapy as a treatment of these nonunions.Twenty-three patients with a fracture nonunion in the metaphyseal-diaphyseal region of the fifth metatarsal received high-energy shock wave therapy (2000 to 4000 shocks; energy flux density per pulse, 0.35 mJ/mm2), and twenty other patients with the same type of fracture nonunion were treated with intramedullary screw fixation. The numbers of fractures that were healed at three and six months after treatment in each group were determined, and treatment complications were recorded.Twenty of the twenty-three nonunions in the shock wave group and eighteen of the twenty nonunions in the screw fixation group were healed at three months after treatment. One of the three nonunions that had not healed by three months in the shock wave group was healed by six months. There was one complication in the shock wave group (post-treatment petechiae) and eleven complications in the screw-fixation group (one refracture, one case of cellulitis, and nine cases of symptomatic hardware).Both intramedullary screw fixation and shock wave therapy are effective treatments for fracture nonunion in the metaphyseal-diaphyseal region of the fifth metatarsal. Screw fixation is more often associated with complications that frequently result in additional surgery.Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.