Energised fragments from explosions are the most common wounding mechanism in conflicts and terrorist attacks. Skin covers the vast majority of the human body and is therefore the first anatomical component to be penetrated by fragments, however, its resistance to penetration largely has not been taken into account in models of injury. In this study, an experimental model for ballistic testing of skin is established and a suitable skin simulant for studying resistance to penetration is determined. Fragment-simulating projectiles were fired at human cadaveric skin and skin-simulant candidates. Tissue responses were quantified by evaluating the impact velocity at 50% risk of skin penetration and perforation, and the depth of penetration in cadaveric tissue or skin-simulant candidates. The results identified a 1.5-mm-thick butyl rubber as a suitable skin simulant across the range of threats tested. The findings can help refine assessment of protective systems and predictive models of injury in an effort to improve outcomes of fragment-penetrating injuries.