PURPOSE: There is emerging evidence that foot orthoses are effective in the management of patellofemoral pain syndrome (PFPS). However, the identification of those most likely to benefit from foot orthoses has not been adequately explored. The aim of this study was to develop a preliminary clinical prediction rule to help identify individuals with PFPS who are most likely to benefit from foot orthoses. METHODS: A total of 60 individuals with PFPS were issued with noncustomized prefabricated foot orthoses containing built-in arch supports and 4° rear foot varus wedging. Patient-reported level of improvement was documented at 12 wk. Potential baseline predictor variables of interest included patient demographics, pain characteristics, footwear motion control properties, foot and ankle characteristics, and functional performance measures. RESULTS: Fourteen (25%) participants reported marked improvement at 12 wk. The number of participants with marked improvement increased to 78% if three of the following four criteria were met: footwear motion control properties score of <5.0 (indicative of less supportive footwear), usual pain <22.0 mm, ankle dorsiflexion range of motion (knee flexed) <41°, and reduced single-leg squat pain when wearing the orthoses. CONCLUSIONS: Individuals with PFPS who wear less supportive footwear, report lower levels of pain, exhibit less ankle dorsiflexion range of motion, and report an immediate reduction in pain with foot orthoses when performing a single-leg squat are more likely to benefit from foot orthoses.