We examined the effects of medially wedged foot orthoses on knee and hip joint mechanics during running in females with and without patellofemoral pain syndrome (PFPS). We also tested if these effects depend on standing calcaneal eversion angle. Twenty female runners with and without PFPS participated. Knee and hip joint transverse and frontal plane peak angle, excursion, and peak internal knee and hip abduction moment were calculated while running with and without a 6° full-length medially wedged foot orthoses. Separate 3-factor mixed ANOVAs (group [PFPS, control] x condition [medial wedge, no medial wedge] x standing calcaneal angle [everted, neutral, inverted]) were used to test the effect of medially wedged orthoses on each dependent variable. Knee abduction moment increased 3% (P = .03) and hip adduction excursion decreased 0.6° (P < .01) using medially wedged foot orthoses. No significant group x condition or calcaneal angle x condition effects were observed. The addition of medially wedged foot orthoses to standardized running shoes had minimal effect on knee and hip joint mechanics during running thought to be associated with the etiology or exacerbation of PFPS symptoms. These effects did not appear to depend on injury status or standing calcaneal posture.