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Previous research has predominantly focused on the biomechanical effects of anterior–posterior foot motion during running, with comparatively less attention given to medial–lateral foot motion and its impact on lower limb biomechanical characteristics. We recruited 18 healthy runners who wore five different types of running shoes: regular shoes (NS), those with a 6 mm and 9 mm medial–lateral height difference in the forefoot (M6, M9), and those with a 6 mm and 9 mm lateral–medial height difference (L6, L9). Biomechanical parameters of lower limb joints during the stance phase of running, including range of motion, peak angular velocity, peak moment, power, and work, were analyzed. We used paired-sample t-tests and one-dimensional statistical parametric mapping (SPM1D) to compare joint biomechanics between shoes with varying height differences and NS. Under the L6 condition, notable differences occurred in the hip and knee flexion–extension moments during landing and push-off, accompanied by a significant increase in ankle dorsiflexion work and a significant decrease in inversion–eversion work. In contrast, the M9 condition resulted in decreased hip flexion–extension peak moment, power, and work in the sagittal plane. These findings indicate that varying forefoot medial–lateral height differences in running shoes significantly impact lower limb joint dynamics during the stance phase, particularly the L6 condition, potentially reducing knee injury risk and aiding gait improvement for overpronators. The findings offer valuable insights for sports injury prevention and athletic footwear design. However, further research is needed to understand the underlying mechanisms and practical implications for sports injury prevention and performance enhancement. Full article