Much is known about running economy while running on level ground surfaces. However, with the dynamic of elevation changes during running, more research is needed to understand how various grades that will favor respective mechanics. PURPOSE: In this study, we focused on determining whether certain running mechanics and anatomy would predict a runner's oxygen uptake between downhill versus uphill running. METHODS: Twenty-one experienced runners completed six 5-min running trials (1 shoe x 3 grades x 2 visits) in a Saucony marathon racing shoe model (Type A) on level (3.83 m/s), uphill (+4% grade at 3.35 m/s), and downhill ( ˆ’4% grade at 4.46 m/s) conditions. These treadmill speeds at each grade were predicted as metabolic equivalents through all grades. We measured submaximal oxygen uptake and carbon dioxide production during the entire trial duration with the last 3 min of each trial being averaged. A best-fitting line was generated through oxygen uptake versus grade to classify whether runners were more economical in uphill or downhill conditions relative to other subjects. The slope of this line indicated whether runners were more economical at uphill or downhill running, where a positive slope represented a more economical uphill versus downhill runner. Various running mechanics were measured using Vicon Nexus and a Bertec treadmill. A linear regression determined any correlations between peak vertical force, stride rate, plantar velocity, and ground time against uphill/downhill running ability. RESULTS: Peak vertical force was the only factor associated with the slope of oxygen uptake versus grade (running grade ability; p < 0.01). The slope of oxygen uptake versus grade averaged 0.076 ± 0.278 ((ml/kg/min) / % grade). CONCLUSION: Runners that naturally prefer a higher peak vertical force when running on level ground led to a lower running grade ability (lower oxygen uptake during downhill versus uphill running).