BackgroundPassive-dynamic ankle–foot orthoses (PD-AFOs) are often prescribed to address plantar flexor weakness during gait, which is commonly observed after stroke. However, limited evidence is available to inform the prescription guidelines of PD-AFO bending stiffness. This study assessed the extent to which PD-AFOs customized to match an individual’s level of plantar flexor weakness influence walking function, as compared to No AFO and their standard of care (SOC) AFO.MethodsMechanical cost-of-transport, self-selected walking speed, and key biomechanical variables were measured while individuals greater than six months post-stroke walked with No AFO, with their SOC AFO, and with a stiffness-customized PD-AFO. Outcomes were compared across these conditions using a repeated measures ANOVA or Friedman test (depending on normality) for group-level analysis and simulation modeling analysis for individual-level analysis.ResultsTwenty participants completed study activities. Mechanical cost-of-transport and self-selected walking speed improved with the stiffness-customized PD-AFOs compared to No AFO and SOC AFO. However, this did not result in a consistent improvement in other biomechanical variables toward typical values. In line with the heterogeneous nature of the post-stroke population, the response to the PD-AFO was highly variable.ConclusionsStiffness-customized PD-AFOs can improve the mechanical cost-of-transport and self-selected walking speed in many individuals post-stroke, as compared to No AFO and participants’ standard of care AFO. This work provides initial efficacy data for stiffness-customized PD-AFOs in individuals post-stroke and lays the foundation for future studies to enable consistently effective prescription of PD-AFOs for patients post-stroke in clinical practice.Trial Registration: NCT04619043.