Background A three-part ankle replacement was developed to achieve compatibility with the natural ligaments by allowing fibers on the medial and lateral sides to remain isometric during passive motion. Unlike all current prostheses, the new design uses nonanatomically shaped components on the tibia and talus and a fully conforming interposed meniscal bearing.Questions/purposes Does this new design restore ankle mobility, improve clinical score, and result in low complication and early revision rates? Patients and Methods We reviewed 51 patients in whom 51 prostheses were implanted in a seven-center trial from July 2003 to July 2006. The mean age of the patients at surgery was 61.5 years (range, 35.1-82.5 years). We used the AOFAS score to assess clinical outcome. We used lateral radiographs to assess function. The minimum followup was 24 months (mean, 30 months; range, 24-48 months). Results The mean preoperative AOFAS score of 38.5 increased to 76.9, 79.1, 76.4, and 79.0 at 12, 24, 36, and 48 months, respectively. We observed a correlation between meniscal bearing movement on the tibial component (mean, 3.4 mm; range, 2-12 mm) and range of flexion at the replaced ankle (mean, 27.48; range, 168-538). We revised one arthroplasty in the second postoperative year for lateral impingement, providing a 3-year cumulative survival rate of 97% and performed one other secondary operation for hindfoot pain. Conclusions These data suggest the new prosthesis can provide short-term restoration of ankle mobility, a good clinical score, and low complication and failure rates. Longer followup with larger numbers is required.