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The purpose of this study was to compare the clinical and radiographic outcomes of total ankle arthroplasty (TAA) in patients with pre-operatively moderate and severe arthritic varus ankles to those achieved for patients with neutral ankles.A total of 105 patients (105 ankles), matched for age, gender, body mass index, and follow-up duration, were divided into three groups by pre-operative coronal plane tibiotalar angle; neutral (< 5°), moderate (5° to 15°) and severe (> 15°) varus deformity. American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, a visual analogue scale (VAS), and Short Form (SF)-36 score were used to compare the clinical outcomes after a mean follow-up period of 51 months (24 to 147).The post-operative AOFAS, VAS scores, range of movement and complication rates did not significantly differ among three groups. However, there was less improvement in the SF-36 score of the severe varus group (p = 0.008). The mean post-operative tibiotalar alignment was 2.6° (0.1° to 8.9°), 3.1° (0.1° to 6.5°) and 4.6° (1.0° to 10.6°) in the neutral, moderate and severe groups respectively. Although the severe varus group showed less corrected alignment than the neutral group, the mean tibiotalar angles of the three groups were within neutral alignment.TAA for moderate and severe varus arthritic deformity showed similar satisfactory clinical and radiographic outcomes as those obtained by patients in the neutral group when postoperative neutral alignment was achieved.