Autonomous Emergency Braking systems with Powered Two-Wheelers (PTW) detection (AEB- PTW) are expected to equip vehicles in the near future. This study aims at prospectively estimating the performance of AEB-PTW in avoiding accidents or mitigating their consequences, based on real-world, representative car-to-PTW French accident data. The same accidents were re-simulated using kinematic models of the vehicles, ideal AEBPTW sensor models and realistic detection-action logics. The effectiveness of AEB-PTW could then be assessed in terms of reduction in fatal, severe, and slight injuries, using injury risk curves that were built from the same accidents sample. Performance results showed that fitting AEB-PTW on cars could potentially lead to halving the most severe PTW users’ casualties in crossing and left turn across path configurations. AEB-PTW performance in car-PTW rear-end accidents was even higher, reaching up to a potential 80% reduction of the most severe casualties. This performance is obtained at the expense of a steep upgrade of AEB sensor settings as compared, for example, to AEB-Pedestrian. To the authors’ knowledge, this is the first attempt at assessing the potential effectiveness of AEB-PTW systems, based on representative accident data, for all levels of injury.