Exoskeletons have the potential to assist users and augment physical ability. To achieve these goals across users, individual variation in muscle activation patterns when using an exoskeleton need to be evaluated. This study examined individual muscle activation patterns during walking with a powered ankle exoskeleton. 60% of the participants were observed to reduce medial gastrocnemius activation with exoskeleton powered and increase with the exoskeleton unpowered during stance. 80% of the participants showed a significant increase in tibialis anterior activation upon power addition, with inconsistent changes upon power removal during swing. 60% of the participants that were able to adapt to the system, did not de-adapt after 5 min. Muscle activity patterns differ between individuals in response to the exoskeleton power state, and affected the antagonist muscle behavior during this early adaptation. It is important to understand these different individual behaviors to inform the design of exoskeleton controllers and training protocols.