OBJECTIVE: To examine the effects of creatine supplementation on the incidence of cramping and injury observed during 1 season of National Collegiate Athletic Association Division IA football training and competition. DESIGN AND SETTING: In an open-label manner, subjects who volunteered to take creatine ingested 0.3 g.kg(-1).d(-1) of creatine for 5 days followed by an average of 0.03 g.kg.(-1)d(-1) after workouts, practices, and games. Creatine intake was monitored and recorded by researchers throughout the course of the study. SUBJECTS: Thirty-eight of 72 athletes (53.0%) participating in the 1999 Division IA collegiate football season from the same university volunteered to take creatine in this study. Subjects trained, practiced, or played in environmental conditions ranging from 15 degrees C to 37 degrees C (mean = 27.26 degrees +/- 10.93 degrees C) and 46.0% to 91.0% relative humidity (mean = 54.17% +/- 9.71%). MEASUREMENTS: Injuries treated by the athletic training staff were recorded and categorized as cramping, heat illness or dehydration, muscle tightness, muscle strains, noncontact joint injuries, contact injuries, and illness. The number of missed practices due to injury and illness was also recorded. Data were analyzed using a 2 x 2 chi(2) test to examine the first reported incidences of cramping and injury for creatine users and nonusers. RESULTS: Creatine users had significantly less cramping (chi(2)(1) = 5.35 P =.021); heat illness or dehydration (chi(2)(1) = 4.09, P =.043); muscle tightness (chi(2)(1) = 5.39, P =.020); muscle strains (chi(2)(1) = 5.36, P =.021); and total injuries (chi(2)(1) = 17.80, P<.001) than nonusers. There were no significant differences between groups regarding noncontact joint injuries (chi(2)(1)= 3.48, P =.062); contact injuries (chi(2)(1) = 0.00, P =.100); illness (chi(2)(1) = 6.82, P =.409); missed practices due to injury (chi(2)(1) = 1.43, P =.233); or players lost for the season (chi(2)(1) = 4.75, P =.491). CONCLUSIONS: The incidence of cramping or injury in Division IA football players was significantly lower or proportional for creatine users compared with nonusers.