OBJECTIVE: This study examined the effects of orthotic materials on running economy, running mechanics, and footwear comfort. DESIGN: A double-blinded randomized crossover study design was used. METHOD: Eighteen athletes ran on an instrumented treadmill for six minutes at speeds corresponding to 10 % below their first ventilatory threshold (average: 9.9 ± 1.3 km/h) in four footwear conditions [control (CON), Ethyl vinyl acetate (EVA), Thermoplastic Polyurethane (TPU), and a combination of EVA and TPU (HYB)]. RESULTS: No differences were found in running economy between conditions (p = 0.099). All custom foot orthoses materials reduced peak heel impact force vs CON (p <
0.002). TPU reduced hysteresis at heel impact vs CON (-47.8 %, p = 0.016). Shorter flight time (-3.8 %, p = 0.016
-3.1 %, p = 0.021) and lower mean vertical loading rate (-4.0 %, p = 0.003
-7.1 %, p <
0.002) occurred for HYB vs TPU and CON, respectively. Higher peak vertical loading rates (+7.4 %, p = 0.002) and earlier impact peaks (-5.7 %, p <
0.002) were found for HYB vs TPU. HYB exhibited longer propulsive phase duration (+2.0 %, p = 0.003) but lower peak propulsive force (-3.3 %, p = 0.009) vs CON. Reduced 'overall comfort' (-26.4 %, p = 0.004), 'comfort of heel cushioning' (-43.3 %, p <
0.002), and 'comfort of forefoot cushioning' (-18.3 %, p = 0.048) was found for HYB vs TPU, but 'comfort of forefoot cushioning' (+48.0 %, p = 0.032) showed an increase vs EVA. CONCLUSIONS: Combining materials could enhance comfort during running causing subtle changes in running mechanics. Overall, neither EVA, TPU nor their combination significantly improved running economy compared to CON.