The purpose of this study was to examine the effects of creatine supplementation on the incidence of injury observed during 3-years of NCAA Division IA college football training and competition. In an open label manner, athletes participating in the 1998-2000 football seasons elected to take creatine or non-creatine containing supplements following workouts/practices. Subjects who decided to take creatine were administered 15.75 g of creatine for 5 days followed by ingesting an average of 5 g/day thereafter administered in 5-10 g doses. Creatine intake was monitored and recorded by research assistants throughout the study and ranged between 34-56% of players during the course of the study. Subjects practiced or played in environmental conditions ranging from 8-40 degrees C (mean 24.7 +/- 9 degrees C) and 19-98% relative humidity (49.3 +/- 17%). Injuries treated by the athletic training staff were recorded and categorized as cramping, heat/dehydration, muscle tightness, muscle strains/pulls, noncontact joint injuries, contact injuries, and illness. The number of missed practices due to injury/illness was also recorded. Data are presented as the total number of treated injuries for creatine users/total injuries observed and percentage occurrence rate of injuries for creatine users for all seasons. The incidence of cramping (37/96, 39%), heat/dehydration (8/28, 36%), muscle tightness (18/42, 43%), muscle pulls/strains (25/51, 49%), non-contact joint injuries (44/132, 33%), contact injuries (39/104, 44%), illness (12/27, 44%), number of missed practices due to injury (19/41, 46%), players lost for the season (3/8, 38%), and total injuries/missed practices (205/529, 39%) were generally lower or proportional to the creatine use rate among players. Creatine supplementation does not appear to increase the incidence of injury or cramping in Division IA college football players.