Anterior cruciate ligament injuries are more prevalent in female athletes than in male athletes. Basketball is a high-risk sport for anterior cruciate ligament injury in female athletes. This study was conducted to observe the effect of a foot orthosis on the knee ligament injury rate in female basketball players at one US university. One hundred fifty-five players on the women's basketball team were observed for knee ligament injury from 1992 to 2005. Athletes in the 1992-1993 to 1995-1996 school years (July-June) did not receive a foot orthosis and served as the control group; the treatment group comprised the athletes during the 1996-1997 to 2004-2005 school years (July-June). Athletes in the treatment group received a foot orthosis before participating in basketball. Data analysis included knee ligament injury rates and a comparison of injury rates with an incidence density ratio. Athletes in the control group had three collateral ligament injuries and three anterior cruciate ligament injuries, for an injury rate of 0.50 for both the anterior cruciate ligament and collateral ligaments. Athletes in the treatment group had four collateral ligament injuries and one anterior cruciate ligament injury, for an injury rate of 0.29 for the collateral ligaments and 0.07 for the anterior cruciate ligament. Athletes in the control group were 1.72 times more likely to sustain a collateral ligament injury and 7.14 times more likely to sustain an anterior cruciate ligament injury than the treatment group. Foot orthoses may contribute to a decreased knee ligament injury rate in female collegiate basketball players.