In persons with calf muscle weakness, walking energy cost is commonly increased due to persistent knee flexion and a diminished push-off. Provided ankle-foot orthoses (AFOs) usually lower walking energy cost. To maximize the reduction in energy cost, AFO bending stiffness should be individually optimized, but this is not common practice. Therefore, we aimed to evaluate whether individually stiffness-optimized AFOs reduce walking energy cost compared to conventional AFOs in persons with non-spastic calf muscle weakness and, secondarily, whether stiffness-optimized AFOs improve walking speed and gait biomechanics. Thirty-seven persons with non-spastic calf muscle weakness using a conventional AFO were included. Participants were provided a new, individually stiffness-optimized AFO. Walking energy cost, speed and gait biomechanics were assessed, at delivery and 3-months follow-up. Stiffness-optimized AFOs reduced walking energy cost with 9.2% (-0.42J/kg/m, 95%CI: 0.26 to 0.57) compared to the conventional AFOs while walking speed increased with 5.2% (+0.05m/s, 95%CI: 0.03 to 0.08). In bilateral affected persons the effects were larger compared to unilateral affected persons (difference effect energy cost: 0.31J/kg/m, speed: +0.09m/s). Although individually gait biomechanics changed considerably, no significant group differences were found (p > 0.118). We demonstrated that individually stiffness-optimized AFOs considerably and meaningfully reduced walking energy cost compared to conventional AFOs, which was accompanied by an increase in walking speed. Especially in bilateral affected persons large effects of stiffness-optimization were found. The individual differences in gait changes substantiate the recommendation that the AFO bending stiffness should be individually tuned to minimize walking energy cost.