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The purpose of this study was to describe the effects of running speed and slope on metatarsophalangeal (MTP) joint kinematics. 22 male and female runners underwent 3D motion analysis on an instrumented treadmill at three different speeds (2.5 m/s, 3.0 m/s, 3.5 m/s). At each speed, participants ran at seven slope conditions (downhill: -15%, -10%, -5%, level, and uphill: +5%, +10%, +15%). We found a significant main effect (p < 0.001) of running speed and slope on peak MTP dorsiflexion and a running speed by slope interaction effect (p < 0.001) for peak MTP dorsiflexion velocity. These findings highlight the need to consider running intensity and environmental factors like running surface inclination when considering MTP joint mechanics and technological aids to support runners.