Sprain of the ankle syndesmosis is a much rarer injury than lateral ankle sprain, but appears to be a more serious injury, often resulting in persistent disability. Many clinical diagnostic tests are described in the literature, but reliability and accuracy have not been adequately investigated. Therefore, using MRI as the reference standard, a study was conducted to determine the accuracy of the clinical presentation of injury and the four most commonly used tests; the dorsiflexion-external rotation stress test, squeeze test, dorsiflexion lunge with compression test, and syndesmosis ligament palpation. The study revealed that we cannot rely on a single test to diagnose ankle syndesmosis injury, but a combination of sensitive and specific tests should raise the level of suspicion for ankle syndesmosis injury. Following injury, an investigation of prognosis found that conservatively treated ankle syndesmosis injuries took an average of 62 days to recover; four times longer than lateral ankle sprain (15 days). A lower vertical jump height and a higher score on the sport specific subscale of the FABQ were promising as prognostic factors, being moderately well correlated with recovery. A novel, easy-to-use device was developed to standardise performance of the heel rise test, a common measure of plantarflexion endurance. The device was tested for its reliability and showed excellent inter-rater reliability. Limits of agreement were less than two repetitions in 90% of cases. Finally, a prospective study of intrinsic and extrinsic predictors of ankle syndesmosis injury was conducted in football players. Of the 202 players, 6% sustained an ankle syndesmosis injury. No significant predictors of injury were identified. Potential predictors of injury are the vertical jump test and the Star Excursion Balance Test. Participants who sustained an injury during the season jumped higher (VJ) and reached further (SEBT) than participants who did not sustain an injury.