Introduction: People with haemophilia (PwH) suffer from knee and ankle joint pain, but the association with structural damage remains underexplored. They report activity limitations but it is unclear which factors contribute to lower limb activity limitations (LL-AL). Aims: This study aimed (i) to analyse the association between ankle joint pain and structure and (ii) explore the contribution of haemophilia-related, individual and psychological factors to LL-AL in PwH. Methods: This study included 104 moderate/severe PwH. Ankle pain intensity was assessed with a numeric rating scale and pain sensitivity with algometry (pressure pain threshold (PPT A )). Ankle structure was assessed with MRI (IPSG-MRI) and ultrasound (HEAD-US), joint health with the Haemophilia Joint Health Score (HJHS). The HAL-LOWCOM subscore evaluated LL-AL. A Spearman correlation analysed the correlation between ankle pain and structure. The contribution of haemophilia-related factors (joint health, overall pain (Brief Pain Inventory-Pain Severity (BPI-PS)), functional status (2-Minute-Walking-Distance, Timed Up and Go); individual factors (age, BMI) and psychological factors (fear and avoidance beliefs over physical activity (FABQ-PA) and work (FABQ-Work), anxiety and depression) to LL-AL was explored using a regression analysis.Valérie-Anne Chantrain and Sylvain Guillaume contributed equally to this study.