ABSTRACTThe role of trunk orientation during uneven running is not well understood. This study compared the running mechanics during the approach step to and the step down for a 10 cm expected drop, positioned halfway through a 15 m runway, with that of the level step in 12 participants at a speed of 3.5 m s−1 while maintaining self-selected (17.7±4.2 deg; mean±s.d.), posterior (1.8±7.4 deg) and anterior (26.6±5.6 deg) trunk leans from the vertical. Our findings reveal that the global (i.e. the spring-mass model dynamics and centre-of-mass height) and local (i.e. knee and ankle kinematics and kinetics) biomechanical adjustments during uneven running are specific to the step nature and trunk posture. Unlike the anterior-leaning posture, running with a posterior trunk lean is characterized by increases in leg angle, leg compression, knee flexion angle and moment, resulting in a stiffer knee and a more compliant spring-leg compared with the self-selected condition. In the approach step versus the level step, reductions in leg length and stiffness through the ankle stiffness yield lower leg force and centre-of-mass position. Contrariwise, significant increases in leg length, angle and force, and ankle moment, reflect in a higher centre-of-mass position during the step down. Plus, ankle stiffness significantly decreases, owing to a substantially increased leg compression. Overall, the step down appears to be dominated by centre-of-mass height changes, regardless of having a trunk lean. Observed adjustments during uneven running can be attributed to anticipation of changes to running posture and height. These findings highlight the role of trunk posture in human perturbed locomotion relevant for the design and development of exoskeleton or humanoid bipedal robots.