Previous work has demonstrated an improvement in running economy during sustained running on a lower body positive pressure treadmill, but neuromuscular and spatiotemporal measures have only been investigated during short-duration running bouts on these devices. The current study sought to replicate the noted metabolic response and investigate whether neuromuscular and/or spatiotemporal adaptations underlie the noted improvements in running economy. Cross-sectional. Fifteen trained runners (11 males and 4 females) ran three 15-minute trials with 30% bodyweight support at 70% of the speed that elicited their peak oxygen consumption while running on a standard treadmill. A series of 1-way analyses of variance with repeated measures were used to explore differences in dependent variables over the 45minutes of running. Dependent variables included oxygen consumption, root-mean-square electromyography of the vastus medialis and medial gastrocnemius during stance, and spatiotemporal parameters. Oxygen consumption decreased after the initial exposure, with no further reductions after 20minutes. Root-mean-square electromyography of the vastus medialis and medial gastrocnemius also decreased over time, with no further reductions after 20 and 10minutes, respectively. No differences in spatiotemporal parameters were found. Future research should provide sufficient time for runners to develop a more economical gait pattern prior to collecting dependent variables, and previous findings using lower body positive pressure treadmills may need to be reconsidered. Athletes using these devices for training or rehabilitation should note that increased economy will lower the intensity of a given treadmill setting over time.