Background:American football is an extremely physical game with a much higher risk of injury than other sports. While many studies have reported the rate of injury for particular body regions or for individual injuries, very little information exists that compares the incidence or severity of particular injuries within a body region. Such information is critical for prioritizing preventative interventions.Purpose:To retrospectively analyze epidemiological data to identify the most common and most severe foot and ankle injuries in collegiate men’s football.Study Design:Descriptive epidemiology study.Methods:Injury data were obtained from the National Collegiate Athletic Association (NCAA) Injury Surveillance System (ISS) for all foot and ankle injuries during the 2004-2005 to 2008-2009 seasons. Injuries were analyzed in terms of incidence and using multiple measures of severity (time loss, surgeries, medical disqualifications). This frequency and severity information is summarized in tabular form as well as in a 4 × 4 quantitative injury risk assessment matrix (QIRAM).Results:The rate of foot and ankle injuries was 15 per 10,000 athletic exposures (AEs). Five injuries were found to be responsible for more than 80% of all foot and ankle injuries: lateral ankle ligament sprains, syndesmotic (high ankle) sprains, medial ankle ligament sprains, midfoot injuries, and first metatarsophalangeal joint injuries. Ankle dislocations were found to be the most severe in terms of median time loss (100 days), percentage of surgeries (83%), and percentage of medical disqualifications (94%), followed by metatarsal fractures (38 days, 36%, and 49%, respectively) and malleolus fractures (33 days, 41%, and 59%, respectively). Statistical analysis suggests that the 3 measures of severity are highly correlated (r > 0.94), thereby justifying the use of time loss as a suitable proxy for injury severity in the construction of the QIRAM.Conclusion:Based on the QIRAM analysis, the 5 highest risk injuries were identified based on both incidence and severity (ankle dislocations, syndesmotic sprains, lateral ankle ligament sprains, metatarsal fractures, and malleolus fractures). A better understanding of the relative incidence and severity of these injuries will allow coaches, trainers, and researchers to more effectively focus their preventative interventions.