The purpose of this study was to determine if biomechanical data obtained in studies on cadavers correlates with clinical results in the surgical treatment of stage IV pronation-external rotation (PER-IV) ankle fractures. We surgically treated 20 patients who sustained isolated PER-IV ankle injuries and followed 18 of the patients for an average of 2.5 years. Radiographs were evaluated using previously established methods, and clinical outcome was based on the criteria of Cedell. Eleven patients sustained a PER-IV injury with a medial malleolus fracture; 2 required a syndesmosis screw due to poor medial fixation. Good or excellent results were obtained in 90% of the patients in this group; the poor outcome of 1 patient was due to the development of reflex sympathetic dystrophy. Seven patients had a PER-IV injury with a deltoid ligament tear; because of widening of the syndesmosis, 1 patient required an early operation (within 1 week), and 2 patients required late operations (after 1 month). None of these patients should have required a syndesmosis screw based on biomechanical studies. Good or excellent results were obtained in 71% of the patients in this group. We conclude that the biomechanical data concerning placement of a syndesmosis screw in PER-IV ankle fractures does not correlate with in vivo outcome when a deltoid ligament injury occurs. A screw that stabilizes the distal tibiofibular syndesmosis should probably be placed in patients who sustain PER-IV injuries with deltoid ligament ruptures regardless of the level of the fibula fracture.