The forefoot (FF) running pattern has been recently advocated to improve running economy and prevent overuse injuries compared to the rearfoot (RF) pattern. However, these claims have not been supported by empirical evidence. The purpose of this dissertation was to investigate the potential advantages of RF and FF patterns to improve running economy and reduce injury risk in 20 natural RF and 20 natural FF runners. The first study found that the RF group was more economical when performing the RF pattern at a slow, medium, and fast speed vs. FF running. Only running at the fast speed resulted in a difference in economy between footfall patterns in the FF group in which RF running was more economical. Therefore, there is no advantage of FF running for improving running economy. The results of the second study indicated that there was a weak to moderate relationship between Achilles tendon (AT) moment arm length and running with either RF or FF patterns. AT force was greater during FF running, which may increase the risk of developing tendon injury. The third study used a modeling approach to find that FF running resulted in greater elastic energy recoil in the gastrocnemius (GA) and the soleus (SO). However, greater mechanical work overall with FF running resulted in no difference in metabolic cost of the GA between footfall patterns but greater metabolic cost of the SO compared to RF running. The fourth study found that shock attenuation was greater during RF running compared to FF running. Greater shock attenuation during RF running was a result of an increased load imposed on the system. Decomposing the vertical ground reaction force in the frequency domain revealed that RF running may have a greater reliance on passive shock attenuation mechanism whereas the FF pattern may have a greater reliance on active shock attenuation mechanisms. These results suggest that previous speculation that the FF running pattern is more economical was not substantiated. It is likely that each footfall pattern exposes a runner to different types of injuries, rather than one footfall pattern being more injurious than another.