The focus of this study was to determine the effect of different positive posterior heel flare (PPHF) configurations on muscle activation of the tibialis anterior, as well as the effect of the posterior heel flare on several kinetic and kinematic variables during running. The impetus for this study was to identify a possible factor associated with the development of exercise-induced (El) anterior compartment syndrome, in an attempt to reduce the risk of injury among distance runners. The hypothesis was that the presence of a PPHF may result in an increase in activation of the muscles in the anterior compartment, and an increase in the dorsiflexion moment demands. A total of 43 subjects (19 women, 24 men) were tested in two running shoes with different PPHF configurations: Saucony Grid Trigon (11 ± 1 degree) and Asics Gel Cumulus (2 ± 1 degree). All of the subjects were recreationally active, rearfoot strikers. No gender by PPHF interactions existed for any of the dependent variables. The results of this study indicated that the presence of a PPHF caused a statistically significant increase in ankle dorsiflexion angle at heel strike (p<0.001), a decrease in the slope of the vertical ground reaction force (vGRF) (p=0.001), a decrease in the mean vGRF (p=0.013), and a decrease in the peak posterior GRF (p=0.043). No statistically significant difference was found in muscle activation of the tibialis anterior (p=0.064), however, the data trends indicated that muscle activation increased with the presence of a PPHF. Men had increased running speed, peak posterior GRF, and mean anterior-posterior GRF, while the women showed an increase in knee flexion angle as well as muscle activation. The presence of a PPHF affects individuals differently. Individuals use different movement strategies to deal with the PPHF, resulting in different kinematic and kinetic changes. The varying response to the PPHF may not decrease the risk of developing El anterior compartment syndrome. Based on the results of this study, the presence of a PPHF caused changes in kinematic and kinetic variables and muscle activation, which could potentially be one cause of El anterior compartment syndrome.