Background: Although studies have demonstrated the effect of anemia severity on postoperative complications after arthroplasties of the shoulder, hip, and knee, no studies have investigated the effect on total ankle arthroplasty (TAA). The objective was to determine the influence of preoperative anemia severity on complications following TAA. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) was queried from 2006 to 2019 for patients undergoing TAA. Utilizing the World Health Organization (WHO) definitions of anemia, patients were stratified into 3 cohorts: nonanemia (hematocrit >36% for women, >39% for men), mild anemia (hematocrit 33%-36% for women, 33%-39% for men), and moderate to severe anemia (hematocrit <33% for both women and men). Demographics, comorbidities, length of stay, and short-term (30-day) postoperative complications were compared between groups. Bivariate analyses, including χ2 and analysis of variance, and multivariable logistical regression were performed. Results: After exclusion, 1490 patients (1313 nonanemia [88.1%], 154 mild anemia [10.3%], and 23 moderate/severe anemia [1.6%]) were included. Increasing severity of anemia was associated with an increased average hospital length of stay (1.84 vs 2.19 vs 2.78 days, P < .001) and rate of reoperation (0.38% vs 3.90% vs 4.35%, P < .001). There was a statistically significant increase in wound disruptions (0.15% vs 1.95% vs 4.35%, P = .001), minor complications (1.52% vs 4.55% vs 8.70%, P = .008), major complications (1.98% vs 5.84% vs 4.35%, P < .033), and any complications (3.50% vs 10.39% vs 13.04%, P = .001) between groups. Multivariate analysis identified mild and moderate/severe anemia as a predictor of reoperation and extended length of stay (P ≤ .033). Discussion: Preoperative anemia is a modifiable risk factor for medical and surgical complications within 30 days of TAA. Medical optimization prior to surgical intervention is necessary in patients undergoing TAA. Level of Evidence: Level III: Retrospective comparative study