Preoperative talar valgus deformity increases the technical difficulty of total ankle replacement (TAR) and is associated with an increased failure rate. Deformity of ≥15° has been reported to be a contraindication to arthroplasty. The goal of the present study was to determine whether the operative procedures and clinical outcomes of TAR for treatment of end-stage ankle arthritis were comparable for patients with preoperative talar valgus deformity of ≥15° as compared to those with <15°. We will describe the evolving surgical technique being utilized to tackle these challenging cases. Fifty ankles with preoperative coronal-plane tibiotalar valgus deformity of ≥15° “valgus” group) and 50 ankles with valgus deformity of <15° (“control” group) underwent TAR. The cohorts were similar with respect to demographics and components used. All TARs were performed by a single surgeon. The mean duration of clinical follow-up was 5.5 years (minimum two years). Preoperative and postoperative radiographic measurements of coronal-plane deformity, Ankle Osteoarthritis Scale (AOS) scores and Short Form (SF)-36 scores were prospectively recorded. All ancillary (intraoperative) and secondary procedures, complications and measurements were collected. The AOS pain and disability subscale 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. The valgus group underwent more ancillary procedures during the index surgery (80% vs 26%). Tibio-talar deformity improved significantly toward a normal weight-bearing axis in the valgus group. Secondary postoperative procedures were more common in the valgus group (36%) than the controls (20%). Overall, re-operation was not associated with poorer patient outcome scores. Metal component revision surgery occurred in seven patients (three valgus and four controls). These revisions included two deep infections (2%), one in each group, which were converted to hindfoot fusions. Therefore, 94% of the valgus group retained their original components at final follow-up Thus far, this is the largest reported study that specifically evaluates TAR with significant preoperative valgus alignment, in addition to having the longest follow-up. Satisfactory midterm results were achieved in patients with valgus mal-alignment of ≥15°. The valgus cohort required more procedures during and after their TAR, as well as receiving more novel techniques to balance their TAR. Whilst longer term studies are needed, valgus coronal-plane alignment of ≥15° should not be considered an absolute contraindication to TAR if the associated deformities are addressed.