Objective <p>To evaluate the risk of lateral ankle sprain (LAS) related to bone anatomical variations of the distal tibiofibular syndesmosis (DTS) and the height of both malleolar articular surfaces.</p> Materials and methods <p>This retrospective cohort study included patients undergoing evaluation and assessment of quantitative parameters of the DTS and height of both malleolar articular surfaces in ankle MRI. Of the 216 patients included, 116 suffered LAS (53.7%). The measurements of the DTS were: anterior facet length of the fibular notch (<i>a</i>), posterior facet length of the fibular notch (<i>b</i>), angle between the anterior and posterior facets (<i>c</i>), fibular notch depth (<i>d</i>), tibial thickness (<i>e</i>), and fibular thickness (<i>f</i>). A subjective morphological analysis of the DTS was also assessed. The measurements of the malleolar articular surface length were: medial malleolar articular surface height (<i>h</i>), lateral malleolar articular surface height (<i>i</i>), and width of the talar dome articular surface (<i>j</i>).</p> Results <p>Evaluating the DTS, patients with LAS showed a greater <i>c</i> (<i>p</i> &lt; 0.001), a higher <i>a</i>/<i>b</i> (<i>p</i> = 0.013), and a lower <i>d</i>/<i>e</i> (<i>p</i> &lt; 0.001). A plane DTS was also found to be a risk factor for sprain. Additionally, patients with LAS exhibited a lower <i>i</i>/<i>j</i> (<i>p</i> = 0.003). Indeed, the values of <i>c</i>, <i>a</i>/<i>b</i>, and <i>i</i>/<i>j</i> were independent predictors of LAS (<i>p</i> &lt; 0.001, <i>p</i> = 0.015, <i>p</i> = 0.011).</p> Conclusion <p>Anatomical factors of the DTS and lateral malleolus articular surface were predictors of the presence of LAS, mainly the angle and ratio between the anterior and the posterior facets and the ratio between the lateral malleolar height and the width of the talar articular surface.</p> Critical relevance statement <p>Lateral ankle sprains are one of the most common musculoskeletal injuries, and the predisposing anatomical factors are not clear. This study correlates anatomical variants of the distal tibiofibular syndesmosis and the height of both malleoli with lateral ankle sprain.</p> Key Points <p><UnorderedList Mark="Bullet"> <ItemContent> <p>What specific bony variations in the distal tibiofibular syndesmosis and malleolar-talus relationship may predispose individuals to lateral ankle sprains?</p> </ItemContent> <ItemContent> <p>A shallow fibular notch, flat-type syndesmosis, and a lower lateral malleolar height/talar width ratio are more often found in first lateral ankle sprains.</p> </ItemContent> <ItemContent> <p>Understanding these anatomical variations may aid in injury prevention and improve risk assessment.</p> </ItemContent> </UnorderedList></p> Graphical Abstract <p></p>