BACKGROUND: Foot deformity, flat feet, and the use of ill-fitting footwear are common in children and adolescents with Down syndrome (DS). The aim of this study was to determine whether these observations are associated with foot-specific disability in this group. METHODS: A cross-sectional study design. Foot structure (foot posture determined using the Arch Index, presence of hallux valgus and lesser toe deformities) and footwear fit (determined by length and width percentage differences between the participant's foot and footwear) were assessed in 50 participants with DS (22 females, 28 males) aged five to 18 with a mean (SD) age of 10.6 (3.9) years. Foot-specific disability was determined using the parent-reported Oxford Ankle Foot Questionnaire for Children (OxAFQ-C). Associations between foot structure and footwear fit with the four domains (Physical, School and play, Emotional and Footwear) of the OxAFQ-C were determined using multivariate regression modelling. RESULTS: The mean (SD) Arch Index was 0.29 (0.08), and the prevalence of flat feet, hallux valgus and lesser toe deformities was 76%, 10% and 12% respectively. Few participants wore footwear that was too short (10%), but the use of footwear that was too narrow was common (58%). The presence of hallux valgus was significantly associated with increased disability for the OxAFQ-C School and play domain scores. The use of narrow-fitting footwear was significantly associated with increased levels of disability for the OxAFQ-C Physical, School and play, and Emotional domains. However, these variables only explained between 10% to 14% of the variance in the OxAFQ-C domain scores. There were no significant associations between foot structure and footwear fit with the OxAFQ-C Footwear domain scores. CONCLUSIONS: Flatter feet and lesser toe deformities are not associated with foot-specific disability in children and adolescents with DS. Hallux valgus is associated with foot-specific disability during school and play activities. Ill-fitting footwear (too narrow) is common and is associated with foot-specific disability. Further research is required to identify if the relationship between narrow-fitting footwear and foot-specific disability is causal, and to identify other factors associated with foot-specific disability in children and adolescents with DS.