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Preoperative talar varus deformity increases the technical difficulty of total ankle replacement and is associated with an increased failure rate. Deformity of >20° has been reported to be a contraindication to arthroplasty. We determined whether clinical outcomes of total ankle replacement in patients with ankle arthritis and preoperative talar varus deformity of ≥10° were comparable with those of patients with varus deformity of <10°.Thirty-six ankles with preoperative coronal-plane tibiotalar varus deformity of ≥10° (“varus” group) and thirty-six prospectively matched ankles with varus deformity of <10° (“neutral” group) underwent total ankle replacement. Preoperative and postoperative evaluations included AOFAS (American Orthopaedic Foot & Ankle Society) ankle-hindfoot scores, Ankle Osteoarthritis Scale (AOS) scores, Short Form (SF)-36 scores, and radiographic measurements of coronal-plane deformity.The cohorts were similar with respect to age, sex, operatively treated side, body mass index, and components used, and the mean duration of clinical follow-up was 34.7 months. Eighteen (50%) of the ankles in the varus group had a preoperative varus deformity of ≥20°. Patients in the varus group underwent more ancillary procedures during the index surgery to achieve a plantigrade foot. The AOFAS score improved by a mean of 57.2 points in the varus group and 51.5 points in the neutral group. The AOS pain and disability component scores decreased significantly in both groups. The improvement in AOS and SF-36 scores did not differ significantly between the groups at the time of the final follow-up. Tibiotalar deformity improved significantly toward a normal weight-bearing axis in the varus group. Thirteen ankles in the varus group and six in the neutral group underwent additional procedures at a later date.Satisfactory results can be achieved in patients with varus malalignment of ≥10°, which should not be considered a contraindication to total ankle replacement. Complication rates can be reduced by utilizing meticulous surgical technique and taking care to address all causes of the varus deformity, particularly through osteophyte debridement, correction of cavus deformity, and soft-tissue balancing.Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.