Exoskeletons that make running easier could increase users’ physical activity levels and provide related health benefits. In this paper, we present the design of a portable, powered ankle exoskeleton that assists running and uses lightweight and compact twisted string actuators. It has limited durability at this stage of development, but preliminary results of its power to mass density and potential for reducing the metabolic cost of running are promising. The exoskeleton can provide high peak power of 700 W per leg, 7 times more than prior twisted-string devices, and high peak torques of 43 Nm. Kinetostatic and dynamic models were used to select mass-optimal components, producing a device that weighs 1.8 kg per leg and 2.0 kg in a backpack. We performed preliminary tests on a single participant to evaluate the exoskeleton performance during both treadmill running and outdoor running. The exoskeleton reduced metabolic energy use by 10.8% during treadmill running tests and reduced cost of transport by 7.7% during outdoor running tests compared to running without the device. Unfortunately, the twisted string wore out quickly, lasting an average of 4 min 50 s before breaking. This exoskeleton shows promise for making running easier if string life challenges can be addressed.