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Purpose: American football is widely played by college student-athletes throughout the United States; however, the associated injury risk is greater than in other team sports. Numerous factors likely contribute to this risk, yet research identifying these risk factors is limited. The present study sought to explore the relationship between playing experience and position on injury risk in NCAA Division I college football players. Methods: Seventy-six male college student-athletes in the football program of an American NCAA Division I university participated. Injuries were recorded over 2 consecutive seasons. Players were characterized based on college year (freshman, sophomore, junior, or senior) and playing position. The effect of playing experience and position on injury incidence rates was analyzed using a generalized linear mixed-effects model, with a Poisson distribution, log-linear link function, and offset for hours of training exposure or number of in-game plays (for training and game injuries, respectively). Results: The overall rates of non-time-loss and time-loss game-related injuries were 2.1 (90% CI: 1.8-2.5) and 0.6 (90% CI: 0.4-0.8) per 1000 plays, respectively. The overall rates of non-time-loss and time-loss training-related injuries were 26.0 (90% CI: 22.6-29.9) and 7.1 (90% CI: 5.9-8.5) per 1000 h, respectively. During training, seniors and running backs displayed the greatest risk. During games, sophomores, juniors, and wide receivers were at greatest risk. Conclusions: Being aware of the elevated injury risk experienced by certain player groups may help coaches make considered decisions related to training design and player selection. [ABSTRACT FROM AUTHOR]