OBJECTIVES: Injuries in sports, including professional American football, are a major public health problem affecting millions of young and adult athletes around the world each year. While most injuries are minor, some end seasons, careers, and may even result in long-term disability. No outcomes databases exist that focus on injuries in the National Football League (NFL). We sought to develop a database that’s longitudinal and includes key injury impact outcomes. METHODS: Four years of data including information on any player that played 1+ regular season games between 2010 and 2013 were adapted from NFL.com, ESPN.com, TSN.com and several other reputable online sources. Five different and unique data types, all capable of being merged with one another and used in longitudinal analyses, were stored as SAS datasets: Player Background (e.g., age, weight, position), Games Played, NFL Injury Report, Injured Reserve List, and Schedule and Conditions (e.g., field surface, weather conditions, referee).  Data from the NFL Injury Report and Injured Reserve List contain every significant injury to NFL players during the 4-year period including concussions, knees, ankles, hamstrings, etc. Injury Impacts include games missed due to injuries as well as season- and career-ending injuries. RESULTS: Data on 3,193 unique NFL players are included in the database. About 7,700 player-seasons are captured that cover nearly 91,000 player-games. About 18,500 Injury Reports are recorded on these players resulting in more than 6,000 missed games. In addition, almost all 959 Injured Reserve List injuries are season-ending and significantly raise the risk of ending a player’s career. CONCLUSIONS: The L-NFL-III database can be a useful tool for epidemiological and outcomes research related to injuries in the NFL. In 4-year longitudinal analyses, this database was successful in identifying a large number of missed games due to injuries, as well other critical outcomes including season- and career-ending injuries.