BACKGROUND The knee joint is the second most commonly injured body site and the leading cause of high school sports-related surgeries. Knee injuries are among the most economically costly sports injuries and may require subsequent surgery or extensive and expensive rehabilitation. OBJECTIVE To report the incidence, risk, and severity of high school knee injuries across sports, genders, and type of exposure. METHODS Descriptive epidemiology study. METHODS During the 2005-2006 and 2006-2007 school years, 100 US high schools were randomly selected for a nationally representative sample. Certified athletic trainers tracked injuries using an online injury surveillance system, High School RIO, in 9 high school sports. RESULTS There were 1383 knee injuries reported during 3,551131 athlete exposures for a rate of 3.89 knee injuries per 10,000 athlete exposures. Although boys had a higher overall rate of knee injury (rate ratio, 1.38; confidence interval, 1.22-1.55), girls were twice as likely to sustain knee injuries requiring surgery (major knee injuries) than were boys (injury proportion ratio, 1.98; confidence interval, 1.45-2.70) and twice as likely to incur noncontact major knee injuries (injury proportion ratio, 1.98; confidence interval, 1.23-3.19) as were boys. Although illegal play was identified as a contributing factor in only 5.7% of all knee injuries, 20% of knee injuries resulting from illegal play required surgery. CONCLUSIONS Knee injury rates and patterns varied by sport, gender, and type of exposure. Identified gender differences included differences in injury rates, injury severity, and basic injury mechanism. Further surveillance is crucial for the development of targeted, evidence-based injury prevention strategies to reduce the morbidity and economic impact of knee surgeries.