The aim of this study was to assess the energy cost and physical strain of daily activities in adolescents and young adults with myelomeningocele (MMC) compared with peers without a disability. Eighteen participants with MMC aged between 16 and 30 years (13 males, five females; mean age 21y 4mo [SD 4y 8mo]) and 18 age- and sex-matched non-disabled participants performed several standardized activities. Energy cost was assessed by oxygen uptake expressed per unit time (all activities) and per metre (walking and wheelchair use at preferred speed). Physical strain was calculated by dividing energy cost by aerobic capacity. For all activities no difference was found in energy cost per unit time between ambulatory participants with MMC and comparison participants. Energy cost per metre walking at preferred speed in participants with MMC was 0.26ml/kg/m (SD 0.08), and in comparison participants was 0.20ml/kg/m (SD 0.03); p=0.08. Non-ambulatory participants with MMC had lower energy cost (per unit time and per metre) during wheelchair use than comparison participants during walking (p<0.05). For most activities, physical strain was 1.4 to 2 times higher in participants with MMC than in comparison participants (p<0.05). In conclusion, energy cost per unit time of daily activities was not increased in participants with MMC. However, energy cost per metre during walking at preferred speed and physical strain were higher than in peers without disability.