Background United States high school soccer participation increased 5 fold over the last 30 years. With increased participation comes increased injury incidence. Hypothesis High school soccer injury patterns will vary by gender and type of exposure. Study Design Descriptive epidemiologic study. Methods Soccer-related injury data were collected over the 2005–2006 and 2006–2007 school years from 100 nationally representative United States high schools via Reporting Information Online (RIO, an Internet-based sports-related injury surveillance system). Results Participating certified athletic trainers reported 1524 soccer injuries during 637 446 athlete exposures (AEs), for an injury rate of 2.39 per 1000 AEs, corresponding to a nationally estimated 807 492 soccer-related injuries during the 2005–2006 and 2006–2007 seasons. The injury rate per 1000 AEs was greater during competition (4.77) than practice (1.37) (rate ratio [RR] = 3.49; 95% confidence interval [CI], 3.15–3.87). Overall, the most frequent diagnoses were incomplete ligament sprains (26.8%), incomplete muscle strains (17.9%), contusions (13.8%), and concussions (10.8%). The most commonly injured body sites were the ankle (23.4%), knee (18.7%), head/face (13.7%), and thigh/upper leg (13.1%). Similar proportions of boys (57.9%) and girls (53.9%) returned to activity in <1 week. During competition, girls sustained complete knee ligament sprains requiring surgery at a rate of 26.4 per 100 000 AEs, higher than the rate among boys during competition (1.98 per 100 000 AEs) (RR = 13.3; 95% CI, 3.15–56.35) and among girls during practice (2.34 per 100 000 AEs) (RR = 11.3; 95% CI, 4.31–29.58). Player-to-player contact was more common among competition injuries (injury proportion ratio [IPR] = 2.42; 95% CI, 2.01–2.92), while noncontact mechanisms were more common among practice injuries (IPR = 2.39; 95% CI, 1.90–3.01). Conclusions High school soccer injury patterns vary by gender and type of exposure. Identifying such differences in injury patterns is the important first step in the development of evidence-based, targeted injury prevention efforts.