Background: It remains controversial whether significant preoperative tibiotalar varus and valgus deformity should be contraindications for total ankle replacement (TAR). The primary aim of this systematic review was to analyze the influence of preoperative tibiotalar varus and valgus alignment on the survival of TAR. Methods: The databases MEDLINE and Embase were searched from onset through September 2018. Two authors performed study selection and data extraction using a predefined data extraction tool. Implant survival in the alignment groups was reported as “revisions per 100 component years.” Additional procedures, complications, and revisions were also reported. Assessment of the methodological quality was performed using the Newcastle-Ottawa Scale (NOS). Results: In total, 17 studies were considered eligible, in which a total of 1692 TARs were included from 1627 patients. The weighted mean follow-up was 52.4 (range, 1-147) months. The neutral alignment group included 711 TARs, the varus group included 545 TARs, and the valgus group included 332 TARs. Total revisions were 52, 37, and 36 in the preoperative tibiotalar neutral, varus, and valgus alignment groups, respectively. Revisions per 100 observed component years were 1.6, 1.7, and 2.5 in the preoperative tibiotalar neutral, varus, and valgus alignment groups, respectively. A total of 129 complications and 447 additional procedures were reported in 601 TARs. Conclusion: There was a strong indication that preoperative varus alignment in the coronal plane had a comparable implant survival to neutral alignment. Preoperative valgus alignment demonstrated a more negative influence on implant survival. Level of evidence: Level III, systematic review.