Metastatic disease to long bones is common and often requires stabilization to treat or prevent fracture. Intramedullary fixation is used in many metaphyseal and diaphyseal lesions. The goal of this study was to investigate the causes of and risk factors for reconstructive failure in intramedullary fixation of metastatic disease. We performed a retrospective review of 112 consecutive reconstructions for metastatic disease treated with an isolated intramedullary nail. There were 81 reconstructions in the femur, 25 in the humerus, and 6 in the tibia. All included patients were followed until death or reconstructive failure. All surviving patients had a minimum 2-year follow-up.Ten failures required construct revision. Median time to revision was 17.9 months (range, 3-93 months). The causes of failure included surgeon error, tumor progression, nonunion, and hardware failure. Patients with short survival times (P< .001) or a diagnosis of lung cancer (P=.029) were unlikely to fail. Revision was required in 6 solitary lesions (P=.012), 3 cases of lymphoma (P=.002), 3 cases of progressive renal cell carcinoma (P=.040), and 2 radiation-associated fractures (P=.007).Intramedullary stabilization is a successful operation for appropriate lesions. Failures may be minimized with proper implant selection and surgical technique, resection or curettage of renal cell carcinoma, avoidance of radiation-associated fractures, and overestimating patient survival.