Individuals with Down syndrome (DS) show reduced gait stability that may increase the metabolic rate (MR) during over-ground walking and alter their energetic cost per unit distance (EC transport ) to speed relationship. If so, the preferred walking speed (PWS) of people with DS may coincide with their speed at minimal EC transport , reflecting energetic optimization. This study therefore examined whether MR and EC transport during over-ground walking differ between individuals with and without DS and whether PWS minimizes their EC transport . Expired gases were collected from 18 individuals with DS and 18 without during six over-ground walking trials, each lasting 6min, at PWS and at 0.51, 0.76, 1.01, 1.26, and 1.51m/s. Gross- and net-MR, and gross- and net-EC transport were expressed in dimensionless form. Energetically optimal walking speeds and minimal gross- and net-EC transport were determined from the gross- and net-EC transport to speed curves for each participant. Individuals with DS showed higher gross-MR, net-MR, gross-EC transport , and net-EC transport . PWS minimized gross-EC transport in participants with DS, but not in those without. PWS did not minimize net-EC transport in either group. Therefore, gross-EC transport minimization during over-ground walking may determine PWS when impairments alter the gross-EC transport to speed relationship.