Background. Modular endoprostheses today represent a standard treatment option in the management of musculoskeletal tumors of the lower extremities. Long-term results of these reconstructions, however, are often limited by the course of the underlying disease. We therefore report our experiences in cancer patients with megaprostheses of the lower limb after a minimum of 15 years. Materials and Methods. 62 patients, 34 men and 28 women, with a mean age of 26 years (median, 20; range, 6–83) were included in this investigation with a mean follow-up of 230 months (median, 228; range, 180–342). Endoprosthetic reconstructions of the proximal femur (11), the distal femur (28), the total femur (2) or the proximal tibia (21) were indicated for osteosarcoma (43), chondrosarcoma (5), malignant fibrous histiocytoma (3) or other tumors (11). All patients have received either a KMFTR (22) or a HMRS (40) modular prosthesis; 23 patients had a muscle flap, 14 had a fibular transposition osteotomy and 4 have received an artificial LARS ligament for soft-tissue reconstruction. Results. 7 patients (11.3%) died throughout the follow-up period, but none succumbed to primary disease. One patient (1.6%) developed a local recurrence after 31 months that was resected. Overall, 56 patients (90.3%) underwent revision of their prosthesis; 50 (80.7%) had multiple revisions up to a maximum of 12 operations (mean, 3 per patient). The median overall prosthetic survival to first revision was 40 months; the corresponding 5-, 10- and 15-year survival rates were 35.5%, 14.5% and 12.9%, respectively. 3 patients (5.4%) had an infection, 8 (14.3%) had a soft-tissue related failure, 30 (53.6%) had a mechanical or structural failure and 15 (26.8%) had an aseptic loosening. The 15-year survival rates of these respective endpoints were 87.1% for infection, 79.0% for soft-tissue related failure, 32.3% for mechanical or structural failure and 56.5% for aseptic loosening. 59 patients (95.2%) have retained their prosthesis; 2 patients (3.2%) underwent secondary amputation due to an irresolvable complication, another one (1.6%) for a second malignancy. Conclusion. Modular prosthetic reconstructions of the lower extremities have a high revision rate in the long-term, primarily due to mechanical failures. Given that patients survive their malignant disease the rate of secondary implant removal, however, tends to be low, providing satisfactory function and body integrity. Further advances in implant design, soft tissue management and infection prophylaxis are required to reduce revision rates