Study Design Retrospective cohort. Background Star Excursion Balance Test (SEBT) performance differs by sport in healthy collegiate athletes, and lower extremity injury rates also vary by sport, sex, and athletic exposure. The relationship between SEBT performance and injury risk has not been evaluated with consideration of these additional variables, which may be necessary to fully describe the relationship between SEBT performance and injury risk. Objectives To assess the association between preseason SEBT performance and noncontact injury occurrence to the knee or ankle in Division I collegiate athletes when controlling for sport, sex, and athletic exposure. Methods Star Excursion Balance Test performance, starting status, and injury status were reviewed retrospectively in National Collegiate Athletic Association Division I collegiate athletes from a single institution. A total of 147 athletes were healthy at the time of preseason SEBT testing and either remained healthy (n = 118) or sustained a noncontact injury to the knee or ankle (n = 29) during their sport's subsequent competitive season. Side-to-side asymmetries were calculated in each direction as the absolute difference in reach distance between limbs. Star Excursion Balance Test reach distances and asymmetries were compared between groups using multivariable regression, controlling for sport, sex, and athletic exposure (starter, nonstarter). Receiver operating characteristic curves were used to determine optimal sensitivity and specificity for significant models. Results When controlling for sport, sex, and athletic exposure, SEBT side-to-side asymmetry in the anterior direction, expressed as an absolute or normalized to limb length, discriminated between injured and noninjured athletes (area under the curve greater than 0.82). Conclusion Assessing side-to-side reach asymmetry in the anterior direction of the SEBT may assist in identifying collegiate athletes who are at risk for sustaining noncontact injuries to the knee or ankle. Level of Evidence Prognosis, level 2b. J Orthop Sports Phys Ther 2017;47(5):339–346. Epub 29 Mar 2017. doi:10.2519/jospt.2017.6974