BACKGROUND: Syndesmotic sprains may be a significant source of missed playing time, especially in football players. Advanced imaging is frequently used to confirm the clinical diagnosis. Our purpose was to evaluate the prognostic ability of MRI in predicting time of disability. METHODS: Training room records from 1993 to 2007 for three National Football League teams were reviewed. Forty-three players were diagnosed with syndesmotic ankle injuries and underwent radiographs and magnetic resonance imaging. A blinded musculoskeletal radiologist interpreted all images. Players with fractures were excluded. RESULTS: Thirty-six professional football players were included in the final analysis. Twenty-three players had a positive squeeze test which was correlated with increased missed practices (p = 0.012) and increased missed games (p = 0.01). The average number of games missed was 3.3 (range, 0 to 20) and the average number of practices missed was 16.7 (range, 0 to 114). Four players had isolated injury to the anterior tibio-fibular ligament (AITFL) (MRI Grade I). Five players had injury to the AITFL and interosseous ligament (MRI Grade II). Twenty-four players sustained injury to the AITFL, interosseous ligament, and posterior inferior tibio-fibular ligament (MRI Grade III). Three players had Grade III injuries with additional injury to the deltoid ligament (MRI Grade IV). Increasing grade of injury was positively correlated with increased number of missed games (p = 0.033) and missed practices (p = 0.002). CONCLUSION: MRI can be useful to help delineate the injury pattern and associated injuries, and may be useful in predicting time of disability using a grading system. Positive squeeze test can also be useful to determine prognosis.