OBJECTIVES: Despite the health benefits of organized sports, high school athletes are at risk for lower extremity sports-related injuries (LESRIs). The authors documented the epidemiology of LESRIs among U.S. high school athletes. METHODS: Via two-stage sampling, 100 U.S. high schools were randomly selected. During the 2005 school year, LESRIs in nine sports were reported: boys' baseball, football, and wrestling; girls' softball and volleyball; and boys' and girls' basketball and soccer. The authors calculated rates as the ratio of LESRIs to the number of athlete exposures. National estimates were generated by assigning injuries a sample weight based on the inverse probability of the school's selection into the study. RESULTS: Among high school athletes in 2005, 2,298 of 4,350 injuries (52.8%) were LESRIs. This represents an estimated 807,222 LESRIs in U.S. high school athletes in nine sports (1.33/1,000 athlete exposures). Football had the highest LESRI rate for boys (2.01/1,000) and soccer the highest for girls (1.59/1,000). Leading diagnoses were sprains (50%), strains (17%), contusions (12%), and fractures (5%). The ankle (40%), knee (25%), and thigh (14%) were most frequently injured. Fractures occurred most often in the ankle (42%), lower leg (29%), or foot (18%). Girls with ligamentous knee injuries required surgery twice as often as boys (67% vs. 35%; p < 0.01). Girls had 1.5 times the proportion of season-ending LESRIs of boys (12.5% vs. 8%; p < 0.01). CONCLUSIONS: While LESRIs occur commonly in high school athletes, team- and gender-specific patterns exist. Emergency department staff will likely encounter such injuries. To optimize prevention strategies, ongoing surveillance is needed.