Background: Outcomes of total ankle replacement for the treatment of end-stage ankle arthritis continue to improve. Debate continues whether a mobile-bearing total ankle replacement (MB-TAR) or a fixed-bearing total ankle replacement (FB-TAR) is superior, with successful outcomes reported long term for MB-TAR and at intermediate- to long-term follow-up for newer generation FB-TAR. Although comparisons between the 2 total ankle designs have been reported, to our knowledge, no investigation has compared the 2 designs with a high level of evidence. This prospective, randomized controlled trial conducted at a single institution compares patient satisfaction, functional outcomes, and radiographic results of the mobile-bearing STAR and the fixed-bearing Salto-Talaris in the treatment of end-stage ankle arthritis. Methods: Between November 2011 and November 2014, adult patients with end-stage ankle osteoarthritis failing nonoperative treatment were introduced to the study. With informed consent, 100 patients (31 male and 69 female, average age 65 years, range 35-85 years) were enrolled; a demographic comparison between the 2 cohorts was similar. Exclusion criteria included inflammatory arthropathy, neuropathy, weight exceeding 250 pounds, radiographic coronal plane deformity greater than 15 degrees, or extensive talar dome wear pattern (“flat-top talus”). Prospective patient-reported outcomes, physical examination, and standardized weightbearing ankle radiographs were obtained preoperatively, at 6 and 12 months postoperatively, and then at yearly intervals. Data collection included visual analog pain score, Short Form 36, Foot and Ankle Disability Index, Short Musculoskeletal Functional Assessment, and American Orthopaedic Foot & Ankle Society ankle-hindfoot score. Surgeries were performed by a nondesign team of orthopedic foot and ankle specialists with total ankle replacement expertise. Statistical analysis was performed by a qualified statistician. At average follow-up of 4.5 years (range, 2-6 years) complete clinical data and radiographs were available for 84 patients; 7 had incomplete data, 1 had died, 4 were withdrawn after enrolling but prior to surgery, and 4 were lost to follow-up. Results: In all outcome measures, the entire cohort demonstrated statistically significant improvements from preoperative evaluation to most recent follow-up with no statistically significant difference between the 2 groups. Radiographically, tibial lucency/cyst formation was 26.8% and 20.9% for MB-TAR and FB-TAR, respectively. Tibial settling/subsidence occurred in 7.3% of MB-TAR. Talar lucency/cyst formation occurred in 24.3% and 2.0% of MB-TAR and FB-TAR, respectively. Talar subsidence was observed in 21.9% and 2.0% of MB-TAR and FH-TAR, respectively. Reoperations were performed in 8 MB-TARs and 3 FH-TARs, with the majority of procedures being to relieve impingement or treat cysts and not to revise or remove metal implants. Conclusion: With a high level of evidence, our study found that patient-reported and clinical outcomes were favorable for both designs and that there was no significant difference in clinical improvement between the 2 implants. The incidence of lucency/cyst formation was similar for MB-TAR and FH-TAR for the tibial component, but the MB-TAR had greater talar lucency/cyst formation and tibial and talar subsidence. As has been suggested in previous studies, clinical outcomes do not necessarily correlate with radiographic findings. Reoperations were more common for MB-TAR and, in most cases, were to relieve impingement or treat cysts rather than revise or remove metal implants. Level of Evidence: Level I, prospective randomized study.