We report on a user study that compared muscle fatigue experienced when using a large multi-touch display in horizontal and vertical configurations over a one-hour period. Muscle fatigue is recognized as the reduction in a muscle’s capacity to generate force or power output and was measured objectively and subjectively before and after a puzzle-solving task. While subjective measures showed a significant level of overall arm muscle fatigue after the task for both configurations, objective measures showed a significant level of muscle fatigue on the middle deltoids and the non-dominant extensor digitorum for the vertical configuration only. We discuss the design implications of these findings and suggest relevant future areas of investigation.