Background: Prior studies on the INBONE II and Salto Talaris total ankle arthroplasty (TAA) systems have reported promising outcomes for both implants. This retrospective study aimed to compare the midterm differences between INBONE II and Salto Talaris TAA. Methods: Between 2007 and 2015, a total of 44 INBONE II consecutive cases and 85 Salto Talaris consecutive cases had minimum 5-year clinical and radiographic follow-up. Preoperative and midterm survivorship, postoperative Foot and Ankle Outcome Score (FAOS), and radiographic measures including tibiotalar alignment (TTA), medial distal tibial angle (MDTA), and sagittal tibial angle (STA) were compared. Results: Survivorship to revision was 97.6% (95% CI, 93.1%-100%) for the INBONE II group and 97% (95% CI, 93%-100%) for the Salto Talaris group ( P = .93). Survivorship to reoperation was significantly different: 95.5% for the INBONE II and 76.4% for Salto Talaris ( P = .021). Postoperative FAOS pain ( P = .01), symptoms ( P = .004), and sports activity ( P = .02) scores were significantly higher in the INBONE II group. The INBONE group had greater preoperative deformity (varus TTA P < .001, valgus TTA P = .02, valgus MDTA P = .005). Conclusion: Although both implants had similar longevity and postoperative alignment, the INBONE II resulted in greater clinical improvement and fewer reoperations than the Salto Talaris at midterm follow-up. Level of Evidence: Level III, retrospective cohort study.