Background: Despite multiple techniques to improve syndesmotic reduction accuracy, syndesmotic malreduction in unstable ankle fractures remains prevalent. We performed a prospective, observational study to assess the ability of intraoperative multidimensional fluoroscopy to lead a surgeon to change the syndesmotic reduction obtained by conventional fluoroscopic techniques with the goal of achieving an accurate reduction. Methods: Thirty patients with unilateral malleolar ankle fractures and syndesmotic instability were enrolled. Following fixation of the malleollar fractures, the syndesmosis was provisionally reduced. Once the surgeon believed acceptable reduction was obtained by comparison with the contralateral, uninjured ankle mortise and lateral fluoroscopic images, provisional fixation was used to maintain reduction. Intraoperative, multidimensional fluoroscopy was used to generate cross-sectional images to assess the reduction. The surgeon then decided if a change in the reduction was needed, and fixation proceeded per surgeon preference. Postoperative bilateral computed tomography (CT) scans of the ankles were used to assess the reduction. Results: The main outcome recorded was syndesmotic reduction change by the attending surgeon following 3-dimensional (3D) fluoroscopic imaging. The secondary outcome was syndesmotic reduction accuracy on postoperative CT scan. Fourteen of 30 patients had intraoperative reduction change following 3D fluoroscopic imaging. Three of 30 patients had residual malreduction compared with the contralateral ankle on bilateral postoperative CT scan. Conclusion: Intraoperative 3D fluoroscopy frequently led the surgeon to change the syndesmotic reduction obtained by conventional techniques and provided additional information not available with 2-dimensional fluoroscopy. A 10% syndesmotic malreduction rate was obtained with this technique. Level of Evidence: Diagnostic level II, prospective comparative study.