Anchorage of segmental replacement prostheses in diaphyseal bone remains a challenge in lower limb reconstructions. We developed and studied a new prosthesis design that features an intramedullary anchorage system for which finite element analysis predicted favorable bone remodeling. We retrospectively analyzed the cases of all patients who underwent implantation of the new stem. Their data were prospectively collected. Twenty-four patients (25 prosthetic reconstructions using diaphyseal fixation of the prosthesis) had 18 primary implantations and 7 revision cases. At a mean follow- up of 61 months, TESS (Toronto Extremity Salvage Score) and MSTS (Musculoskeletal Tumor Society Rating Scale score) were 80% and 65% that of a normal extremity, respectively. SF-36 (36-Item Short-Form Health Survey) Mental and Physical scores were 54 and 44 points, respectively. Minimum follow-up was 31 months (mean, 61 months; range, 31-107 months). Radiographic evaluation (1991 International Symposium of Limb Salvage [ISOLS] Radiological Implant Evaluation System) revealed 65% excellent and 35% good bone remodeling around the implant as a whole, 65% excellent and 35% good results for the anchorage proper, and 70% excellent and 30% good findings for lucencies at the bone-metal interface. Two patients (1 traumatic event) developed a loose stem. The results support the expectations as shown by finite element analysis - that the risk for loosening is reduced and that favorable bone remodeling occurs around the stem over time.