Purpose We determined the effect of custom foot orthotics manufactured from ethyl-vinyl acetate (EVA) and expanded thermoplastic polyurethane (TPU) materials, both compared to a control condition (CON; shoes only) during repeated sprints on running mechanical alterations. Methods Eighteen males performed eight, 5-s sprints with 25-s recovery on an instrumented sprint treadmill in three footwear conditions (EVA, TPU and CON). Mechanical data consisted of continuous (step-by-step) measurement of running kinetics and kinematics, which were averaged for each sprint for further analysis. Results Distance ran in 5 s decreased from first to last sprint (P < 0.001), yet with higher sprints 1-8 values for both EVA (P = 0.004) and TPU (P = 0.018) versus CON. Regardless of footwear condition, mean horizontal forces, step frequency, vertical and leg stiffness decreased from sprint 1 to sprint 8 (all P < 0.001). Duration of the propulsive phase was globally shorter for both EVA (P = 0.002) and TPU (P = 0.021) versus CON, while braking phase duration was similar (P = 0.919). In the horizontal direction, peak propulsive (P < 0.001), but not braking (P = 0.172), forces also decreased from sprint 1 to sprint 8, independently of conditions. Conclusion Compared to shoe only, wearing EVA or TPU custom foot orthotics improved repeated treadmill sprint ability, yet provided similar fatigue-induced changes in mechanical outcomes. Keyword Insoles • Instrumented treadmill • Running kinematics • Leg-spring behaviour Abbreviations ANOVA Repeated-measures analysis of variance CFO Custom foot orthotics CON Control condition EVA Ethyl-vinyl acetate GRF Ground reaction forces RPE Ratings of perceived exertion RSE Repeated sprint exercise TPU Thermoplastic polyurethane