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Purpose: The aim of this study was to provide a theoretical model to predict the vertical loading rate (VLR) at different slopes and speeds during incline running. Methods: Twenty-nine healthy subjects running at least once a week performed in a randomized order 4-min running trials on an instrumented treadmill at various speeds (8, 10, 12, and 14 km h(-1)) and slopes (- 20%, - 10%, - 5%, 0%, + 5%, + 10%,+ 15%,+ 20%). Heart rate, gas exchanges and ground reaction forces were recorded. The VLR was then calculated as the slope of the vertical force between 20 and 80% of the duration from initial foot contact to the impact peak. Results: There was no difference in VLR between the four different uphill conditions at given running speeds, but it was reduced by 27% at 5% slope and by 54% at 10% slope for the same metabolic demand (similar VO2), when compared to level running. The average VLR measured at maximal aerobic intensity during level running would be decreased by 52.7% at + 5%, by 63.0% at+ 10%, and by 73.3% at+ 15% slope. Moreover, VLR was dependent on the slope in downhill conditions. Conclusion: This study highlights the possibility to use uphill running to minimize rate of mechanical load (i.e., osteoarticular load) from foot impact on the ground and as a time-efficient exercise routine (i.e., same energy expenditure than in level running in less time).