Background: There is sparse information in the literature on the outcome of Maisonneuve-type pronation-external rotation ankle fractures treated with syndesmotic screws. The primary aim of this study was to determine the long-term results of such treatment of these fractures as indicated by standardized patient-based and physician-based outcome measures. The secondary aim was to identify predictors of the outcome with use of bivariate and multivariate statistical analysis. Methods: Fifty patients with pronation-external rotation (predominantly Maisonneuve) fractures were treated with open reduction and internal fixation of the syndesmosis utilizing only one or two screws. The results were evaluated at a mean of twenty-one years after the fracture utilizing three standardized outcomes instruments: (1) the Foot and Ankle Ability Measure (FAAM), (2) the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale, and (3) the Center for Epidemiologic Studies-Depression (CES-D) Scale. Osteoarthritis was graded according to the van Dijk and revised Takakura radiographic scoring systems. Bivariate and multivariate analyses were performed to identify predictors of long-term outcome. Results: Forty-four (92%) of forty-eighty patients had good or excellent AOFAS scores, and forty-four (90%) of forty-nine had good or excellent FAAM scores. Arthrodesis for severe osteoarthritis was performed in two patients. Radiographic evidence of osteoarthritis was observed in twenty-four (49%) of forty-nine patients. Multivariate analysis identified pain as the most important independent predictor of long-term ankle function as indicated by the AOFAS and FAAM scores, explaining 91% and 53% of the variation in scores, respectively. Analysis of pain as the dependent variable in bivariate analyses revealed that depression, ankle range of motion, and a subsequent surgery were significantly correlated with higher pain scores. No firm conclusions could be drawn after multivariate analysis of predictors of pain. Conclusions: Long-term functional outcomes at a mean of twenty-one years after pronation-external rotation ankle fractures treated with one or two syndesmotic screws were good to excellent in the great majority of patients despite substantial radiographic evidence of osteoarthritis in one-half of the patients. The most important predictor of long-term functional outcome was patient-reported pain rather than physician-reported function or posttraumatic osteoarthritis. There was no significant association between radiographic signs of posttraumatic osteoarthritis and perceived pain in the present series. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.