To evaluate the clinical outcomes and complications of segmental prosthetic reconstruction for pathological diaphyseal femoral fractures secondary to metastatic tumors. Between 2011 and 2015, we retrospectively evaluated 16 patients (6 men and 10 women; 64.5 ± 11.4 years old at diagnosis) who underwent prosthetic reconstruction after segmental resection of diaphyseal femoral fractures due to metastatic lesions. Visual analog scale (VAS), functional outcomes, implant-related complications, and Mean postoperative Musculoskeletal Tumor Society (MSTS) score for each patient were collected. The mean length of bone defect was 10.2 ± 2.6 cm (range, 8-16 cm); follow-up was 9 ± 6.8 months (range, 2-25 months) for all patients, and 24 months (23 and 25 months) for the 2 patients still alive. At final follow-up, 14 patients were dead, indicating a mean survival of 6.9 ± 3.6 months (range, 2-14 months). Mean preoperative VAS score was 8.5 ± 1.0, which decreased to 2.5 ± 1.3 at day 2 postoperatively, indicating significant pain relief (P < 0.05). The MSTS score for lower extremities was 84.6% (range, 73%-90%). The range of motion and function of adjacent joints was within the normal limits in all cases. Three patients (33%) developed complications, including aseptic loosening because of disease progression (1), infection (1), and peri-prosthesis fracture (1). These findings demonstrated that this approach greatly relieves pain, and yields satisfactory functional outcomes with fewer complications in patients with pathological femoral fractures secondary to metastatic tumors; however, survival was not significantly improved.