The aim of this study is to evaluate degree and possible major determinants of lower limb disability in joint hypermobility syndrome. Forty patients with joint hypermobility syndrome were studied. Lower limb function was evaluated with the lower limb functional scale (LEFS). Intensity of pain was estimated by the numeric rating scale. Rough results were compared with previously published data for osteoarthritis patients. Within the studied population, comparisons were performed by age, sex, numeric rating scale and Beighton scores. In joint hypermobility syndrome, LEFS score was similar to osteoarthritis, but in the former, comparable values were observed with a ~10 year earlier onset. LEFS scores resulted significantly related to age, pain intensity and Beighton score. No correlation with sex was observed. This study demonstrated that, in joint hypermobility syndrome, disability of lower limbs is remarkable and related to the increase in pain and age and to the decrease in residual joint hypermobility. These preliminary results may be relevant for the identification of more efficient and tailored treatment programs.