OBJECTIVE: To review 16 years of National Collegiate Athletic Association (NCAA) injury surveillance data for men's lacrosse and identify potential areas for injury prevention initiatives. BACKGROUND: During the sample period, the number of sponsoring institutions and the number of participants in men's college lacrosse grew significantly. Overall, an average of 18% of NCAA institutions participated in the annual NCAA Injury Surveillance System data collection for this sport. MAIN RESULTS: Over the sample period, athletes were almost 4 times more likely to sustain injuries in games than in practices (12.58 versus 3.24 injuries per 1000 athlete-exposures [A-Es], rate ratio = 3.9, 95% confidence interval = 3.7, 4.1). Approximately half of all game (48.1%) and practice (58.7%) injuries were to the lower extremity, followed by the upper extremity (26.2% in games, 16.9% in practices), and the head and neck (11.7% in games, 6.2% in practices). In games and practices, the most common injuries were ankle ligament sprains (11.3% and 16.4%, respectively). The disparity among preseason, regular-season, and postseason injuries may be due to athlete acclimatization to the rigors of the sport throughout the season. Changes in helmet design may account for the rise in the concussion rate since the 1995-1996 season. RECOMMENDATIONS: We recommend research into the mechanism of head injuries and the implications of design changes to protective helmets, as well as further investigation of the best designs for shoulder and chest protection.