Background: Ankle sprains are a common injury in collegiate sports. Few studies have examined the epidemiology of individual ligament injuries, specifically the lateral ligament complex (LLC) of the ankle. Purpose: To describe the epidemiology, including the estimated yearly national incidence, of LLC sprains among National Collegiate Athletic Association (NCAA) athletes. Study Design: Descriptive epidemiology study. Methods: Injury surveillance data for 25 sports from the NCAA Injury Surveillance Program (NCAA-ISP) for the academic years 2009-2010 to 2014-2015 were used for analysis. All injuries included for analysis had a diagnosis of an LLC sprain. LLC sprain rates and rate ratios (RRs) with 95% CIs were calculated. From the sample, national estimates of the annual incidence of LLC sprains across the entire student-athlete body from these 25 sports were also calculated. Results: During the 2009-2010 to 2014-2015 academic years, 2429 LLC sprains were reported, for a rate of 4.95 per 10,000 athlete-exposures (AEs). LLC sprains comprised 7.3% of all reported collegiate sports injuries in the NCAA-ISP. Also, an estimated 16,022 LLC sprains occurred annually among the 25 sports. The sports with the highest LLC sprain rates were men's basketball (11.96/10,000 AEs) and women's basketball (9.50/10,000 AEs). Most LLC sprains occurred during practices (57.3%); however, the LLC sprain rate was higher in competitions than in practices (RR, 3.29; 95% CI, 3.03-3.56). Also, 11.9% of LLC sprains were identified as recurrent injuries, with the largest proportions of recurrent LLC sprains being found within women's basketball (21.1%), women's outdoor track (21.1%), women's field hockey (20.0%), and men's basketball (19.1%). In 44.4% of LLC sprains, the athlete returned to play in less than 24 hours; in 3.6%, the athlete required more than 21 days before returning to play (including those who did not return to play at all). Conclusion: LLC sprains were the most commonly reported injury diagnosis among United States collegiate student-athletes. Continued examination of interventions that aim to reduce the incidence, severity, and recurrence of LLC sprains, specifically in women, is warranted.