Background: <p>Fatigue as a result of undertaking heavy tasks in people with pronated feet, a common foot deformity, can alter ground reaction force and muscle activity. In the present study the effect of fatigue induced by running at heart rate deflection point was investigated in people with pronated versus healthy feet.</p> Methods<b>:</b> <p>Fourteen young men with pronated-feet aged 20.21 ± 1.22 and 14 young men with normal-feet aged 21.36 ± 2.30 were required to run at the HRDP level until fatigued. GRF and electromyography (EMG) activities of selected lower limb muscles were recorded before and after fatigue started.</p> Results: <p>We found that the main effects of “group” are significant for peak anterior GRFs during push-off (<i>p</i> = 0.015; Effect size=0.20). Pair-wise comparisons reveal significantly smaller peak anterior GRFs during push-off (<i>p</i> = 0.015; Effect size=1.02) in individuals with pronated feet compared with those with normal feet. Moreover, significant main effects of “fatigue” for peak anterior GRFs during push-off (<i>p</i> = 0.003; <i>d</i> = 0.28) and peak negative free moment amplitude (<i>p</i> = 0.016; Effect size=0.20) are observed. Pair-wise comparisons show a fatigue-related decrease in peak anterior GRFs during push-off (<i>p</i> = 0.003; Effect size=1.25) and peak negative free moment amplitude (<i>p</i> = 0.016; Effect size=1.155) in both groups. There are no significant “group by fatigue” interactions for GRF and for peak free moment amplitudes.</p> Conclusions: <p>Changes in muscle activity and ground reaction force after fatigue might lead to muscles losing their ability to control the foot joints and decreasing peak anterior GRFs during push-off in the pronated feet group.</p>