This clinical retrospective study explored factors associated with distal tibiofibular syndesmosis ossification (TFSO) after ankle fracture fixation. Between August 2012 and January 2015, 172 patients with ankle fractures (121 men) with an average age of 46.6 years (range, 22-71 years) were treated surgically with an average follow-up period of 26 months (range, 16-34 months). According to the Danis-Weber AO classification rubric, 54 fractures were type A, 78 were type B, and 40 were type C. According to the Lauge-Hansen classification, there were 17 supination-adduction (SA) fractures, 98 supination-external rotation (SE) fractures, 31 pronation-external rotation (PE) fractures, and 26 pronation-abduction (PA) fractures. The average injury to operation interval was 4.3 days (6 hours-7 days). Multiple factor analysis was conducted to examine risk factors for TFSO. It was observed in 36 (20.9%) cases (11 complete ossification cases; 25 partial ossification cases). Multivariate logistic regression revealed the following independent risk factors for TFSO were: AO classification, distal tibiofibular syndesmosis separation, and fibular fracture morphology. In conclusion, AO type C fracture, syndesmosis separation, and high fibular fracture were associated with distal TFSO following ankle fracture fixation.