Background: The presence of an interface between the tibial component and the polyethylene insert (PI) in mobile-bearing total ankle arthroplasty (TAA) may allow the talus to adapt its axial position according to the patient’s anatomy. However, little is known about differences of the axial talar rotation between patients following mobile-bearing TAA. Therefore, the aim of this study was to assess the relative axial rotation between the talar and tibial component intraoperatively and after a minimum follow-up of 3 years following mobile-bearing TAA. Methods: The relative axial rotation between the talar and the tibial component was measured intraoperatively in a cohort of 58 patients who underwent mobile-bearing TAA. In addition, it was measured on weightbearing computed tomography (CT) scans in 48 patients after a mean of 6.3 (3.0-16.3) years following mobile-bearing TAA. The pre- and postoperative alignment of the ankle joint/tibial component and hindfoot assessed on conventional radiographs was correlated with the intra- and postoperatively determined relative axial rotation of the talar and tibial component. Results: The mean intra- and postoperative axial talar component position was 1.7 (range, 14 internal to 14 external) and 1.4 (range, 12 internal to 20 external) degrees toward internal when compared to the tibial component ( P = .960). The preoperative sagittal alignment of the distal tibia correlated with the intraoperatively determined relative axial rotation between the talar and the tibial component ( P = .019). Conclusion: The wide range of the relative axial rotation between the tibial and talar component suggests that it is crucial to allow the talus to intraoperatively find a position that corresponds to the patient’s individual anatomy. The fact that the range of axial rotation was similar after a minimum of 3 years measured under weightbearing conditions suggests that structural changes of the osteoarthritic ankle may be the main determining factors for the axial rotational position of the talus. Our findings improve current understanding of proper implant position during TAA. In addition, the current study provides a reliable method to assess the postoperative axial position of the prosthesis components. The high interindividual variability of the relative rotation between the tibial and talar component in the axial plane suggests that axial malpositioning following TAA may be a more common issue than currently expected. Our findings may help to improve the assessment of patients with persistent pain following TAA. Level of Evidence: Level III, comparative series.