The mechanism of action of a foot orthotic is poorly understood. The purpose of this study was to use principal components analysis (PCA) to analyze the effects of a prefabricated foot orthotic on frontal plane knee and ankle mechanics during running. Thirty-one healthy subjects performed running trials with and without a foot orthotic and PCA was performed on the knee and ankle joint angles and moments to identify the dominant modes of variation. MANOVAs were conducted on the retained principal components of each waveform and dependent t tests (P < .05) were performed in the case of significance. Mechanics of the ankle were not affected by the foot orthotic. However, mechanics of the knee were significantly altered as subjects demonstrated an increase in the magnitude of the knee abduction moment waveform in an orthotic condition. Subjects also demonstrated a significant shift in the timing of the knee abduction moment waveform toward later in the stance phase in the orthotic condition. These orthotic effects were not related to subject's foot mobility, measured using the navicular drop test. The mechanism of action of a foot orthotic may be related to their effect on the timing of frontal plane knee loading.