BACKGROUND: This study investigated the extent to which reference frame convention affects the interpretation of how gait modification alters the external knee adduction moment. METHODS: Data were collected from a single male able-bodied subject performing three gait tasks: normal, toe out and medial thrust. The net external moment vector at the knee was expressed in five alternative reference frames: the femur anatomical frame, the proximal tibia anatomical frame, the distal tibia anatomical frame, the laboratory frame and a non-orthogonal knee joint coordinate system. For each reference frame, the knee adduction moment was taken as the component about the frame's anteroposterior axis. FINDINGS: Gait modification and selected reference frame both influenced the calculated knee adduction moment. Furthermore, these two effects were interactive, with the magnitude of the changes in the knee adduction moment produced by toe out and medial thrust gait being highly dependent on selected reference frame. INTERPRETATION: Choice of reference frame for calculating the external knee adduction moment is therefore an important consideration for studies investigating the relative effectiveness of interventions such as gait modification.