More than half of patients with hereditary hemochromatosis (HH) have painful arthritis, often including hindfoot osteoarthritis. Total ankle arthroplasty (TAA) is increasingly recommended for patients with painful ankle osteoarthritis. However, the pain relief and function experienced by patients continues to be debated particularly as compared with ankle fusion. We asked whether (1) the complication rates were low; (2) the components were stable; (3) the patients achieved pain relief; and (4) the patients had satisfactory midterm function, ROM, and quality of life. We retrospectively reviewed all 16 prospectively followed patients (21 implants) with HH who underwent ankle arthroplasty. They had an average age of 59.5 years at the time of surgery. We obtained a visual analog scale for pain, the SF-36, and the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score. Component stability was assessed using weightbearing radiographs. The minimum followup was 3.1 years (average, 5.3 years; range, 3.1-8.6 years). Postoperatively, one patient had d,bridement of a painful cyst on the tibial side and one patient had a subfibular d,bridement with a lateral ligament reconstruction. The tibial and talar components were stable in all ankles. The average pain score decreased from 6.7 (range, 3-10) to 1.9 (range, 0-4). All eight categories of SF-36 score showed improvement. The hindfoot score increased from 46 (range, 22-67) to 84 (range, 74-94). Our data suggest TAA in patients with ankle osteoarthritis secondary to HH is associated with a low risk of postoperative complications and produces pain relief and good function. Level IV, therapeutic case series. See Guidelines for Authors for a complete description of levels of evidence.