Background: Syndesmotic malreduction is common and has been associated to an impaired outcome. Various risk factors for DTFJ malreduction have been postulated. The aims of this study were to assess the DTFJ malreduction rate based on (1) the severity of the syndesmotic injury, (2) the anatomy of the tibial incisura, and (3) the fixation device used in patients treated with suture-button systems. Methods: This retrospective, radiographic study included all adult patients who were treated for an acute, unilateral, and unstable syndesmotic injury with a suture-button system and postoperative bilateral CT imaging. Included were isolated syndesmotic injuries and fracture cases. The number of syndesmotic ligaments injured, that is, 2-ligament (AiTFL+IOL) and 3-ligament (AiTFL+IOL+PiTFL), was rated for each patient. The quality of DTFJ reduction, as well as the anatomy of the tibial incisura, was rated based on the postoperative, bilateral CT images and the intraoperative DTFJ reduction was recalculated based on the drilling-tunnel deviation. The possible influence on the DTFJ malreduction rate was assessed. Results: A total of 147 patients were included, and 94 and 53 patients had a 2- and 3-ligament syndesmotic injury, respectively. In addition, 113 patients were treated with a single-button system, 26 with a double suture-button system, and 8 with a hybrid fixation (suture-button + screw). Malreduction was significantly higher in 3-ligament compared with 2-ligament injuries, both intraoperatively (51% vs 27%; P = .003) and postoperatively (28% vs 11%; P = .006). The tibial anatomy had no significant influence on the malreduction rates. No significant differences were seen per the different fixation devices used independent of the number of ligaments injured. Conclusion: This study did not find an influence of the incisura’s anatomy on the DTFJ malreduction rate. However, we did find that 3-ligament syndesmotic injuries carried a higher risk of intra- and postoperative malreduction compared with 2-ligament injuries. Level of Evidence: Level III, retrospective radiologic study.